Compounds and uses therefor

Abstract

Disclosed are glycanic compounds and their use for treating or inhibiting the development of a viral infection in a subject, especially a coronavirus infection, such as a SARS-CoV-2 infection, or for treating conditions associated with viral infections, such as an acute inflammatory condition, cytokine release syndrome (CRS) or a cytokine storm, severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS).

Description

TITLE OF THE INVENTION “COMPOUNDS AND USES THEREFOR”

[0001] This application claims priority to Australian Provisional Patent Application No. 2023902113 entitled "Compounds and uses therefor" filed 30 June 2023, the contents of which are incorporated herein by reference in their entirety. FIELD OF THE INVENTION

[0002] This invention relates generally to glycanic compounds and their use for treating or inhibiting the development of a viral infection in a subject, especially a coronavirus infection, such as a SARS-CoV-2 infection, or for treating conditions associated with viral infections, such as an acute inflammatory condition, cytokine release syndrome (CRS) or a cytokine storm, severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS). BACKGROUND OF THE INVENTION

[0003] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates.

[0004] Viral infections cause a significant economic and social burden to be placed on society, which has been particularly demonstrated by the recent pandemic caused by the coronavirus, SARS-CoV-2. SARS-CoV-2, is a recently emerged virus that causes an often-fatal respiratory disease, COVID-19. The current pandemic caused by SARS-CoV-2 is a health emergency that requires the development of new vaccines and therapeutics to prevent or treat infections caused by this virus.

[0005] SARS-CoV-2 is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV) (Lu et al., Lancet 2020, 395 (10224), 565-574) and recent studies have demonstrated that SARS-CoV-2 spike protein, like SARS-CoV, uses the angiotensin converting enzyme 2 (ACE2) as a cellular receptor to initiate membrane fusion and infection (Hoffmann et al., Cell 2020181(2): 271–280). SARS-CoV-2 engages the ACE2 receptor with higher affinity binding than SARS-CoV (Wrapp et al., Science 2020, 367 (6483), 1260-1263). A number of other viruses use glycoproteins on their surfaces as fusion proteins to interact with and gain entry into host cells to effect infection, including enveloped viruses such as influenza and human immunodeficiency virus (HIV). Accordingly, the interaction between the viral fusion protein and the host cell ligand is an attractive therapeutic target for a number of important viral infections.

[0006] Glycosaminoglycans (GAGs) are linear polysaccharides of very diverse structures. They occur naturally as the glycan moiety of proteoglycans and play pivotal roles in many biological processes within the human body, including the binding and presentation of certain cytokines / growth factors to their cell surface receptors, thereby enhancing receptor signaling. Glycosaminoglycans within extracellular matrices also sequester certain cytokines, growth factors, chemokines and enzymes in specific locations within tissues. However, GAG interactions with particular cytokines, growth factors, chemokines and enzymes can contribute to physiologically adverse processes such as excessive inflammation, cancer growth and metastasis and various immunological reactions with counterproductive outcomes. Currently, some of the best known GAGs belong to the heparin / heparan sulfate family of sulfated polysaccharides. Heparin is best known for its anticoagulant activity, but more recent data indicates that heparin can also have anti-inflammatory activity. Mechanistically these activities are the result of some of the structures in heparin / heparan sulfates binding to three-dimensional motifs on proteins. Given their ability to bind to and modulate the activity of biological regulators, GAGs have been proposed as potential therapeutic agents.

[0007] However, natural GAGs are not ideal therapeutic agents due to their extreme structural heterogeneity, particularly in their complex sulfation patterns, and the difficulties in isolating specific GAG structural entities. This means, generally the natural GAG structural motifs that best bind particular cytokines, growth factors, chemokines or enzymes are unknown. The synthesis of GAG structures is also extremely complex and the synthesis of even small GAG structures requires many synthetic steps. As the complex sulfation patterns of GAGs contributes to their protein binding characteristics, the multiple synthetic steps cannot be avoided when synthesizing GAGs for therapeutic purposes. Accordingly, GAGs or analogues or mimetics thereof which have more suitable therapeutic properties are desired. SUMMARY OF THE INVENTION

[0008] WO 2018 / 068090 A1 discloses a number of compounds which have improved synthetic routes compared to GAGs and, therefore, more suitable therapeutic properties. The present invention is predicated in part on the discovery of particular compounds that bind to the fusion protein (e.g. the spike protein) of viruses and inhibit the interaction between the fusion protein and the host cell. Accordingly, the Inventors have conceived that such compounds will be useful for treating and inhibiting the development of a viral infection in a subject, especially an infection by a virus expressing a viral fusion protein, such as an enveloped virus infection (e.g. a coronavirus infection, such as a SARS-CoV-2 infection) or for treating conditions associated with viral infections (e.g. a coronavirus infection), such as an acute inflammatory condition, CRS or a cytokine storm, SARS or ARDS.

[0009] In one aspect, there is provided a compound of Formula I, II or III:wherein:L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L2, L5and L14are independently selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X1, X2, X3, X4, X5, X6, X7, X8, X9, X10and X11are independently selected from CH and N; and R1is selected from optionally substituted C2-C12 alkyl, optionally substituted C2-C12 alkenyl and optionally substituted C2-C12 alkynyl.

[0010] In some embodiments, X1-X11are CH.

[0011] In some embodiments, L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene. In particular embodiments, L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are optionally substituted C1-C3 alkylene; especially methylene.

[0012] In some embodiments, L2is selected from optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene. In particular embodiments, L2is optionally substituted C2-C5 alkylene, such as propylene (e.g. n-propylene).

[0013] In further embodiments, L5is selected from optionally substituted C3-C6 alkylene, optionally substituted C3-C6 alkenylene and optionally substituted C6-C6 alkynylene. In specific embodiments, L5is optionally substituted C3-C6 alkylene, especially butylene (e.g. n-butylene).

[0014] In some embodiments, L14is selected from optionally substituted C2-C4 alkylene, optionally substituted C2-C4 alkenylene and optionally substituted C2-C4 alkynylene. In particular embodiments, L14is optionally substituted C2-C4alkylene, especially ethylene.

[0015] In specific embodiments, R1is selected from optionally substituted C6- C10 alkyl, optionally substituted C6-C10 alkenyl and optionally substituted C6-C10 alkynyl. In particular embodiments, R1is optionally substituted C6-C10 alkyl, such as octyl.

[0016] In some embodiments, the compound is a compound of Formula IV:

[0017] In alternative embodiments, the compound is a compound of Formula V:

[0018] In other embodiments, the compound is a compound of Formula VI:

[0019] In particular embodiments, the compound is in the form of a salt, especially wherein the salt is the sodium salt.

[0020] In another aspect, there is provided a pharmaceutical composition comprising a compound of Formula I, II, III, IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof and a pharmaceutically acceptable carrier or diluent.

[0021] Further provided is a compound of Formula I, II, III, IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in therapy.

[0022] In a further aspect, there is provided a method of treating or inhibiting the development of a viral infection in a subject comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject:

[0023] In particular embodiments, the infection is caused by a virus expressing a viral fusion protein, such as an enveloped virus. In some embodiments, the infection is caused by a virus that interacts with an ACE2 polypeptide-expressing cell. While any viral infection is contemplated, in particular embodiments, the viral infection is a coronavirus infection, especially wherein the coronavirus is capable of causing SARS. In some embodiments, the coronavirus is a betacoronavirus, such as one selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0024] In some embodiments, the compound is administered by oral, inhalation, intranasal, topical or intravenous administration.

[0025] While administration of a single compound is contemplated, the invention further contemplates administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the method comprises administering a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0026] In another aspect, there is provided a method of inhibiting the interaction of a virus with an ACE2 polypeptide-expressing cell, comprising, consisting or consisting essentially of contacting the virus with a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0027] In some embodiments, the interaction is one or both of binding of the virus to the cell and entry of the virus into the cell.

[0028] In some embodiments, the cell is a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell. In particular embodiments, the cell is a cell of the respiratory tract.

[0029] In particular embodiments, the virus is a coronavirus, especially wherein the coronavirus is capable of causing SARS. In some embodiments, the coronavirus is a betacoronavirus, such as one selected from a lineage A betacoronavirus, a lineage Bbetacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0030] In some embodiments, the compound is administered by oral, inhalation, intranasal, topical or intravenous administration.

[0031] In some embodiments, the method further comprises administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof. Exemplary embodiments comprise administering a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0032] In a further aspect, there is provided a method of treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

[0033] In some embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0034] In some embodiments, the acute inflammatory condition is associated with presence of CRS or a cytokine storm, especially wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0035] In some embodiments, the subject has CRS and has one or more symptoms selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. In alternative embodiments, the subject has a cytokine storm and has one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof.

[0036] In some embodiments, the acute inflammatory condition is associated with a multisystem inflammatory syndrome in children (MIS-C), for example, wherein the subject has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0037] The association of the acute inflammatory condition with a systemic inflammatory response syndrome (SIRS) is also contemplated. In some embodiments, the subject has Stage 1 SIRS (local reaction), Stage 2 SIRS (early compensatory anti- inflammatory response syndrome (CARS) in an attempt to maintain immunological balance), Stage 3 SIRS (pro-inflammatory SIRS resulting in progressive endothelial dysfunction, coagulopathy, and activation of the coagulation pathway), Stage 4 SIRS (characterized by CARS taking over SIRS, resulting in a state of relative immunosuppression. The individual, therefore, becomes susceptible to secondary or nosocomial infections, thus perpetuating the sepsis cascade), or Stage 5 SIRS (manifests in Multiple organ dysfunction syndrome (MODS) with persistent dysregulation of both SIRS and CARS response).

[0038] In some embodiments, the acute inflammatory condition is associated with acute respiratory distress syndrome (ARDS). In such embodiments, the subject may have one or more symptoms selected from mild, moderate or severe hypoxemia as determined by Partial Pressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end-expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness, rapid breathing, organ failure, chest pain, bluish coloring of nails or lips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation.

[0039] In some embodiments, the acute inflammatory condition is associated with SARS. The subject may have, for example, one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure.

[0040] The invention further provides a method of treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound ofFormula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

[0041] In some embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0042] In particular embodiments, the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0043] In some embodiments, the subject has CRS and has one or more symptoms selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination.

[0044] In some embodiments, the subject has a cytokine storm and has one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof.

[0045] The CRS or cytokine storm may be associated with a MIS-C. In such embodiments, the subject may have one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0046] In some embodiments, the CRS or cytokine storm is associated with a SIRS, such as Stage 1 SIRS, Stage 2 SIRS, Stage 3 SIRS, Stage 4 SIRS or Stage 5 SIRS.

[0047] In some embodiments, the CRS or cytokine storm is associated with ARDS. In these embodiments, the subject may have one or more symptoms selected from mild, moderate or severe hypoxemia as determined by Partial Pressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end-expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness,rapid breathing, organ failure, chest pain, bluish coloring of nails or lips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation.

[0048] In particular embodiments, the CRS or cytokine storm is associated with SARS. For example, the subject may have one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro- inflammatory mediators, vascular leakage and organ failure.

[0049] A further aspect of the invention provides a method of treating SARS in a subject, wherein the SARS is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

[0050] In some embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0051] The subject may have one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro- inflammatory mediators, vascular leakage and organ failure, or any combination thereof.

[0052] In some embodiments, the SARS is associated with presence of CRS or a cytokine storm, for example, wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0053] In some embodiments, the SARS is associated with a MISC-C. In such embodiments, the subject has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0054] The SARS may also be associated with a SIRS. For example, the subject may have Stage 1 SIRS, Stage 2 SIRS, Stage 3 SIRS, Stage 4 SIRS or Stage 5 SIRS.

[0055] Further provided herein is a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating or inhibiting the development of a viral infection in a subject.

[0056] Another aspect provides a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection.

[0057] Further contemplated is a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.

[0058] The invention further provides a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.

[0059] Another aspect provides a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating or inhibiting the development of a viral infection in a subject.

[0060] In a further aspect, there is provided a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection.

[0061] Also contemplated herein is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.

[0062] In another aspect, there is provided a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Figure 1 is an image showing the binding of the SARS-CoV-2 spike protein receptor binding domain (RBD) to ACE2 expressing Calu-3 cells in the presence of G24, G22, G17 or heparin in comparison to cells in the absence of a test compound. RBD presence on the cells was detected by an anti-His antibody (red).

[0064] Figure 2 is a graphical illustration showing the percent foci reduction of Vero E6 Monkey kidney cells in the presence of SARS-CoV-2 virus (Australia / VIC01 / 2020) and the presence and absence of various concentrations of test compound (G4, G17, G19, G22 or G24). Unfractionated heparin (UFH) was used as a comparative compound. This data is from a single first run (run 1).

[0065] Figure 3 is a graphical illustration showing the percent foci reduction of Vero E6 Monkey kidney cells in the presence of SARS-CoV-2 virus (Australia / VIC01 / 2020) and the presence and absence of various concentrations of test compound (G4, G17, G19, G22 or G24). This data is from a single second run (run 2).

[0066] Figure 4 is a graphical illustration showing the inhibition of IL-8 (CXCL8) dependent chemotaxis in dimethylsulfoxide (DMSO)-treated human promyelocytic HL-60 cells in the presence of 50 μg / mL of the test compound (G19, G22 and G24). Heparin was used as a comparative compound. Mean and upper and lower limits are represented. DETAILED DESCRIPTION OF THE INVENTION 1. Definitions

[0067] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, preferred methods and materials are described. For the purposes of the present invention, the following terms are defined below.

[0068] The articles “a” and “an” are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0069] By “about” is meant a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 % to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.

[0070] The term “acute inflammatory condition” as used herein refers to a condition in which acute inflammation is present and represents a rapid, short-lived (minutes to days), relatively uniform response to acute injury characterized by accumulations of fluid, plasma proteins, and neutrophilic leukocytes. In acute inflammation, removal of the stimulus halts the recruitment of monocytes (which become macrophages under appropriate activation) into the inflamed tissue, and existing macrophages exit the tissue via lymphatics. Examples of injurious agents that cause acute inflammation include, but are not limited to, pathogens (e.g. bacteria, viruses, parasites), foreign bodies from exogenous (e.g. asbestos) or endogenous (e.g. urate crystals, immune complexes), sources, and physical (e.g. burns) or chemical (e.g. caustics) agents. Generally, the physiologic changes accompanying acute inflammation encompass four main features: (1) vasodilation, which results in a net increase in blood flow, is one of the earliest physical responses to acute tissue injury; (2) in response to inflammatory stimuli, endothelial cells lining the venules contract, widening the intracellular junctions to produce gaps, leading to increased vascular permeability, which permits leakage of plasma proteins and blood cells out of blood vessels; (3) inflammation often is characterized by a strong infiltration of leukocytes at the site of inflammation, particularly neutrophils (polymorphonuclear cells). These cells promote tissue damage by releasing toxic substances at the vascular wall or in uninjured tissue; and (4) fever, produced by pyrogens released from leukocytes in response to specific stimuli. Other conditions include a reduction in olfactory sensation and adverse effects on the cardiovascular system.

[0071] As used herein, the term “acute respiratory distress syndrome” or “ARDS” refers to a life-threatening lung condition that prevents enough oxygen from getting to the lungs and into the blood. ARDS is also referred to as noncardiogenic pulmonary edema, increased-permeability pulmonary edema, stiff lung, shock lung, or acute lung injury. ARDS can be caused by any major injury to the lung. Some common causes include, without limitation: breathing vomit into the lungs (aspiration), inhaling chemicals, lung transplant, pneumonia, septic shock (infection throughout the body), and trauma.

[0072] The terms “administration concurrently” or “administering concurrently” or “co-administering” and the like refer to the administration of a single composition containing two or more agents, or the administration of each agent as separate compositions and / or delivered by separate routes either contemporaneously or simultaneously or sequentially within a short enough period of time that the effective result is equivalent to that obtained when all such agents are administered as a single composition. By “simultaneously” is meant that the agents are administered at substantially the same time, and desirably together in the same composition. By“contemporaneously” it is meant that the agents are administered closely in time, e.g., one agent is administered within from about one minute to within about one day before or after another. Any contemporaneous time is useful. However, it will often be the case that when not administered simultaneously, the agents will be administered within about one minute to within about eight hours and suitably within less than about one to about four hours. When administered contemporaneously, the agents are suitably administered at the same site on the subject. The term “same site” includes the exact location, but can be within about 0.5 to about 15 centimeters, preferably from within about 0.5 to about 5 centimeters. The term “separately” as used herein means that the agents are administered at an interval, for example at an interval of about a day to several weeks or months. The agents may be administered in either order. The term “sequentially” as used herein means that the agents are administered in sequence, for example at an interval or intervals of minutes, hours, days or weeks. If appropriate the agents may be administered in a regular repeating cycle.

[0073] The term “agent” includes a compound that induces a desired pharmacological and / or physiological effect. The term also encompasses pharmaceutically acceptable and pharmacologically active ingredients of those compounds specifically mentioned herein including but not limited to salts, esters, amides, prodrugs, active metabolites, analogs and the like. When the above term is used, then it is to be understood that this includes the active agent per se as well as pharmaceutically acceptable, pharmacologically active salts, esters, amides, prodrugs, metabolites, analogs, etc. The term “agent” is not to be construed narrowly but extends to small molecules, proteinaceous molecules such as peptides, polypeptides and proteins as well as compositions comprising them and genetic molecules such as RNA, DNA and mimetics and chemical analogs thereof as well as cellular agents.

[0074] The term "alkyl" refers to a straight or branched aliphatic hydrocarbon group, including a C1–C12 alkyl, C2-C12 alkyl, C6-C10 alkyl, C7-C9 alkyl and C8 alkyl (octyl) unless otherwise noted. In particular embodiments, the alkyl is a straight aliphatic hydrocarbon group, such as methyl, ethyl, n-propyl, n-butyl, pentyl, hexyl, heptyl, octyl, and the like.

[0075] As used herein, the term "alkylene" refers to divalent alkyl groups having from 1 to 8 carbon atoms, including from 2 to 8 carbon atoms, from 3 to 6 carbon atoms, from 1 to 5 carbon atoms, from 1 to 3 carbon atoms, from 2 to 5 carbon atoms, and from 2 to 4 carbon atoms. Examples of such alkylene groups include methylene (- CH2-), ethylene (-CH2CH2-), propylene, including n-propylene (-CH2CH2CH2-), butylene, including n-butylene (-CH2CH2CH2CH2-), and the like.

[0076] The term "alkenyl" means an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched (preferably straight), including a C2-C12 alkenyl, C6-C10 alkenyl, C7-C9 alkenyl and C8 alkenyl unless otherwise noted. The group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonenyl.

[0077] As used herein, the term “alkenylene” refers to divalent alkenyl groups having from 2 to 8 carbon atoms, including from 3 to 6 carbon atoms, from 2 to 5 carbon atoms, from 2 to 4 carbon atoms, and from 2 to 3 carbon atoms.

[0078] "Alkynyl" means an aliphatic hydrocarbon group containing at least one carbon-carbon triple bond (e.g. one carbon-carbon triple bond) and which may be straight or branched, preferably straight, including C2-C12 alkynyl, C6-C10 alkynyl, C7-C9 alkynyl and C8 alkynyl unless otherwise noted.

[0079] The term “alkynylene” refers to divalent alkynyl groups having from 2 to 8 carbon atoms, including from 3 to 6 carbon atoms, from 2 to 5 carbon atoms, from 2 to 4 carbon atoms, and from 2 to 3 carbon atoms.

[0080] As used herein, the term “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (or).

[0081] The term “antimicrobial agent” as used herein refers to any agent with antimicrobial activity, i.e., the ability to inhibit or reduce the growth and / or kill a microbe, e.g., by at least about 30%, at least about 40%, at least about 50%, at least about 75%, at least about 90% or more, as compared to in the absence of an antimicrobial agent. The term “antimicrobial agent” encompasses agents that that inhibit or reduce the growth and / or kill a microbe by directly interacting with the microbe and / or cells of the host in which the microbe resides or is located. Non-limiting examples of antimicrobial agents include a silver nanoparticle, a small molecule, a peptide, a peptidomimetic, an antibody or a fragment thereof, a nucleic acid, an enzyme (e.g. an antimicrobial metalloendopeptidase such as lysostaphin), an aptamer, a drug, an antibiotic, a chemical or any entity that can inhibit the growth and / or kill a microbe. Examples of an antimicrobial peptide that can be included in the compositions described herein, include, but are not limited to, mefloquine, venturicidin A, antimycin, myxothiazol, stigmatellin, diuron, iodoacetamide, potassium tellurite hydrate, aDL- vinylglycine, N-ethylmaleimide, L-allyglycine, diaryquinoline, betaine aldehyde chloride, acivcin, psicofuraine, buthionine sulfoximine, diaminopemelic acid, 4-phospho-D- erythronhydroxamic acid, motexafin gadolinium and / or xycitrin or modified versions oranalogues thereof. Representative antimicrobial agents include, antibiotics, antifungals, antiprotozoals, antimalarials, antituberculotics and antivirals, and any mixtures thereof. In some embodiments, the antimicrobial agent is an antiviral agent, which encompasses agents that are effective for inhibiting the formation and / or replication of a virus in a mammal. This includes agents that interfere with either host or viral mechanisms necessary for the formation and / or replication of a virus in a mammal. Such agents can be selected from immunomodulatory agents, inhibitors of a virus polymerase or inhibitors of another target in the virus life cycle. Examples of antiviral agents include a-methyl-1- adamantanemethylamine, hydroxy-ethoxymethylguanine, adamantanamine, 5-iodo-2'- deoxyuridine, trifluorothymidine, AZT, adenine arabinoside, Abacavir, Aciclovir, Acyclovir, Adefovir, Amantadine, Amprenavir, Ampligen, Arbidol, Atazanavir, Atripla, Boceprevir, Cidofovir, Combivir, Darunavir, Delavirdine, Didanosine, Docosanol, Edoxudine, Efavirenz, Emtricitabine, Enfuvirtide, Entecavir, Entry, inhibitors, Famciclovir, Fomivirsen, Fosamprenavir, Foscarnet, Fosfonet, Ganciclovir, Ibacitabine, Imunovir, Idoxuridine, Imiquimod, Indinavir, Inosine, Integrase inhibitor, Interferon type III, Interferon type II, Interferon type I, Interferon, Lamivudine, Lopinavir, Loviride, Maraviroc, Moroxydine, Methisazone, Nelfinavir, Nevirapine, Nexavir, Nucleoside analogues, Oseltamivir, (Tamiflu), Peginterferon alfa-2a, Penciclovir, Peramivir, Pleconaril, Podophyllotoxin, Raltegravir, Ribavirin, Rimantadine, Ritonavir, Pyramidine, Saquinavir, Stavudine, Tenofovir, Tenofovir, disoproxil, lipranavir, Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir, (Valtrex), Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Zalcitabine, Zanamivir, (Relenza), and Zidovudine.

[0082] The terms “angiotensin converting enzyme 2 polypeptide”, “ACE2 polypeptide” and “ACE2” are used interchangeably herein to refer to a polypeptide comprising the amino acid sequence of a precursor ACE2 polypeptide (e.g. the human precursor ACE2 polypeptide set forth in GenBank Accession NP_001358344), or processed form thereof (e.g. a mature ACE2 polypeptide in which the signal peptide, as defined for example by amino acids 1-17, has been removed and / or a carboxy terminal portion, as defined for example by amino acids 709-805, has been removed), or biologically active fragments of a precursor or processed form an ACE2 polypeptide, as well as allelic variants of any of these. The degree and location of glycosylation or other post-translation modifications may vary depending on the chosen host and the nature of the hosts cellular environment.

[0083] As used herein, the term “ACE2 polypeptide-expressing cell” refers to a cell that expresses an ACE2 polypeptide typically on its surface. Representative cells that express an ACE2 polypeptide include myeloid cells of the lungs, arteries, heart, kidney, and intestines. The ACE2-expressing cell is suitably selected from a lung cell (e.g. alveolar cell), an enterocyte, an endothelial cell and an arterial smooth muscle cell. Inspecific embodiments, the ACE2-expressing cell is a cell of the respiratory tract (e.g. a lung cell such as an alveolar cell).

[0084] The term “antagonist” and grammatical equivalents thereof as used herein refer to a molecule that partially or completely inhibits, by any mechanism, an effect of another molecule such as a receptor or intracellular mediator. In the context of the present invention, the term “antagonist” refers to a compound that partially or completely inhibits a fusion protein (e.g. a spike protein) from interacting or forming a complex with a host cell ligand, such as a host cell surface protein (e.g. ACE2). In specific embodiments, the antagonist is a direct antagonist that binds to or otherwise interacts with a viral fusion protein (e.g. a spike protein).

[0085] The term "associated with" when used in relation to conditions associated with a viral infection (e.g. a coronavirus infection) means that the viral infection contributes, either directly or indirectly, to the pathogenesis or progression of the condition, including of one or more symptoms of the condition. The viral infection may, for example, directly lead to the pathogenesis (i.e. development) of the condition or the development of one or more symptoms of the condition. Alternatively or in addition, the viral infection may result in the progression (i.e. worsening) of the condition or one or more symptoms of the condition. Similarly, a condition associated with presence of CRS or a cytokine storm, MIS-C, ARDS, SARS or SIRS is one where the presence of CRS or a cytokine storm, MIS-C, ARDS, SARS or SIRS contributes to the pathogenesis or progression of the condition, including of one or more symptoms of the condition.

[0086] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. Thus, the use of the term “comprising” and the like indicates that the listed integers are required or mandatory, but that other integers are optional and may or may not be present. By “consisting of” is meant including, and limited to, whatever follows the phrase “consisting of”. Thus, the phrase “consisting of” indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of” is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified for the listed elements. Thus, the phrase “consisting essentially of” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements.

[0087] The term “cytokine release syndrome” or “CRS” refers to a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs. It refers to cytokine storm syndromes (CSS) and occurs when large numbers of white blood cells are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. CRS is also an adverse effect of some monoclonal antibody medications, as well as adoptive T-cell therapies. When occurring as a result of a medication, it is also known as an infusion reaction. The term cytokine storm is often used interchangeably with CRS but, despite the fact that they have similar clinical phenotype, their characteristics are different. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset CRS is a cytokine storm, although severe cases of CRS have also been called cytokine storms.

[0088] As used herein, the term “cytokine storm” refers to an excessively activated cytokine cascade or hypercytokinemia, i.e., an excessive or uncontrolled release of pro-inflammatory cytokines, which can be associated with a wide variety of infectious and noninfectious diseases or disorders. Cytokine storm syndromes are associated with a group of disorders (such as, but not limited to, influenza, asthma, hantavirus pulmonary syndrome, SIRS, macrophage activation syndrome, SARS, COVID- 19 and disseminated vascular coagulopathy), representing a variety of inflammatory causes. Typically, the primary symptoms of a cytokine storm are high fever, swelling and redness, extreme fatigue and nausea. In some cases, the immune reaction can result in bleeding, clotting, internal organ injury, or shock, and may be fatal.

[0089] As used herein, the term “dosage unit form” refers to physically discrete units suited as unitary dosages for the subject to be treated, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutically acceptable vehicle.

[0090] By “effective amount”, in the context of treating or preventing a condition is meant the administration of an amount of an agent or composition to an individual in need of such treatment or prophylaxis, either in a single dose or as part of a series, that is effective for the prevention of incurring a symptom, holding in check such symptoms, and / or treating existing symptoms, of that condition. The effective amount will vary depending upon the health and physical condition of the individual to be treated, the taxonomic group of individual to be treated, the formulation of the composition, the assessment of the medical situation, and other relevant factors. It is expected that the amount will fall in a relatively broad range that can be determined through routine trials. Non-limiting symptoms of viral infections (e.g. coronavirus infections) include acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughingincluding dry coughing, sore throat, runny nose, nasal congestion, and, in severe disease, symptoms of systemic inflammatory response syndrome including production of pro-inflammatory mediators, vascular leakage and organ failure.

[0091] The term “fusion protein” as used herein refers to a protein on the surface of a virus that interacts with a protein on the surface of a host cell or the cell membrane of the host cell to effect binding of the virus to the host cell and / or viral entry into the host cell. Exemplary fusion proteins include the spike protein of a coronavirus.

[0092] As used herein, the phrase “inhibit the development of” refers to a prophylactic treatment which increases the resistance of a subject to developing the disease or condition or, in other words, decreases the likelihood that the subject will develop the disease or condition as well as a treatment after the disease or condition has begun in order to reduce or eliminate it altogether or prevent it from becoming worse. This phrase also includes within its scope preventing the disease or condition from occurring in a subject which may be predisposed to the disease or condition but has not yet been diagnosed as having it.

[0093] The term “inhibitor” as used herein refers to an agent that decreases or inhibits at least one function or biological activity of a target molecule, such as a viral fusion protein (e.g. the spike protein).

[0094] The term “interaction”, including its grammatical equivalents, when referring to an interaction between two molecules, refers to the physical contact of the molecules with one another. Generally, such an interaction results in an activity (which produces a biological effect, such as viral binding to a host cell and / or viral entry into a host cell) of one or both of said molecules. The physical contact typically requires binding or association of the molecules with one another and may involve the formation of an induced magnetic field or paramagnetic field, covalent bond formation, ionic interaction (such as, for example, as occurs in an ionic lattice), a hydrogen bond, or alternatively, a van der Waals interaction such as, for example, a dipole-dipole interaction, dipole- induced dipole interaction, induced dipole-induced dipole interaction, or a repulsive interaction, or any combination of the above forces of attraction.

[0095] As used herein, the term “multisystem inflammatory syndrome in children” or “MIS-C” is a rare life-threatening illness where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Children with MIS-C may have a fever and various symptoms, including abdominal (gut) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, or feeling extra tired.

[0096] The term "optionally substituted" as used throughout the specification denotes that the group may or may not be further substituted with one or more non- hydrogen substituent groups. In certain embodiments, the substituent groups are one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl (e.g. methyl or ethyl), C2-C6alkenyl and C2-C6alkynyl, especially halogen and C1-C6alkyl. In some embodiments, the optional substituent groups are one or more groups independently selected from the group consisting of methyl, ethyl and halogen, especially methyl. In exemplary embodiments, each optionally substituted group (e.g. alkylene, alkenylene, alkynylene, alkyl, alkenyl or alkynyl) may be substituted with 1-3 substituents, including 1, 2 or 3 substituents, such as 1, 2 or 3 methyl groups.

[0097] The terms “patient”, “subject”, “host” or “individual” used interchangeably herein, refer to any subject, particularly a vertebrate subject, and even more particularly a mammalian subject, for whom therapy or prophylaxis is desired. Suitable vertebrate animals that fall within the scope of the present disclosure include, but are not restricted to, any member of the subphylum Chordata including primates (e.g. humans, monkeys and apes, and includes species of monkeys such as from the genus Macaca (e.g. cynomolgus monkeys such as Macaca fascicularis, and / or rhesus monkeys (Macaca mulatta)) and baboon (Papio ursinus), as well as marmosets (species from the genus Callithrix), squirrel monkeys (species from the genus Saimiri) and tamarins (species from the genus Saguinus), as well as species of apes such as chimpanzees (Pan troglodytes), rodents (e.g. mice rats, guinea pigs), lagomorphs (e.g. rabbits, hares), bovines (e.g. cattle), ovines (e.g. sheep), caprines (e.g. goats), porcines (e.g. pigs), equines (e.g. horses), canines (e.g. dogs), felines (e.g. cats), avians (e.g. chickens, turkeys, ducks, geese, companion birds such as canaries, budgerigars etc.), marine mammals (e.g. dolphins, whales), reptiles (e.g. snakes, frogs, lizards etc.), and fish. In specific embodiments, the subject is a primate such as a human in need of treating or inhibiting the development of a viral infection. However, it will be understood that the terms “patient,” “subject,” “host” or “individual” do not imply that symptoms are present.

[0098] By “pharmaceutically acceptable carrier” is meant a pharmaceutical vehicle comprised of a material that is not biologically or otherwise undesirable, i.e., the material may be administered to a subject along with the selected active agent without causing any or a substantial adverse reaction. Carriers may include excipients and other additives such as diluents, fillers, detergents, coloring agents, wetting or emulsifying agents, pH buffering agents, preservatives and the like.

[0099] Similarly, a “pharmacologically acceptable” salt, solvate, ester or prodrug of a compound as provided herein is a salt, solvate, ester or prodrug that is not biologically or otherwise undesirable.

[0100] The terms “reduce”, “inhibit”, “decrease”, “prevent”, and grammatical equivalents when used in reference to the level of a substance and / or phenomenon in a first sample relative to a second sample, mean that the quantity of substance and / or phenomenon in the first sample is lower than in the second sample by any amount that is statistically significant using any art-accepted statistical method of analysis. When these terms are used to refer to the action of a compound or agent, the first sample may be a sample in the presence of the compound or agent and the second sample may be a comparative sample without the compound or agent. In one embodiment, the reduction may be determined subjectively, for example when a patient refers to their subjective perception of disease symptoms, such as pain, headache, fatigue, nausea, motor symptoms, coughing, sore throat, nasal congestion, runny nose, etc. In another embodiment, the reduction may be determined objectively, for example when the amount of virus (e.g. viral load) in a sample from a patient is lower than in an earlier sample from the patient. In another embodiment, the quantity of substance and / or phenomenon in the first sample is at least 10% lower than the quantity of the same substance and / or phenomenon in a second sample. In another embodiment, the quantity of the substance and / or phenomenon in the first sample is at least 25% lower than the quantity of the same substance and / or phenomenon in a second sample. In yet another embodiment, the quantity of the substance and / or phenomenon in the first sample is at least 50% lower than the quantity of the same substance and / or phenomenon in a second sample. In a further embodiment, the quantity of the substance and / or phenomenon in the first sample is at least 75% lower than the quantity of the same substance and / or phenomenon in a second sample. In yet another embodiment, the quantity of the substance and / or phenomenon in the first sample is at least 90% lower than the quantity of the same substance and / or phenomenon in a second sample.

[0101] As used herein, the terms “salts” and “prodrugs” include any pharmaceutically acceptable salt, ester, hydrate or any other compound which, upon administration to the recipient, is capable of providing (directly or indirectly) a compound of the invention, or an active metabolite or residue thereof. The term “pharmaceutically acceptable salts” refers without limitation to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form (e.g. by reacting the free base group with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Representative acid addition salts includeacetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate and valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. The pharmaceutically acceptable salts of the present invention include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. In particular embodiments, the salt is the sodium salt. Lists of suitable salts are found in, for example, Remington: The Science and Practice of Pharmacy, Loyd V. Allen, Jr (Ed), The Pharmaceutical Press, London, 22ndEdition, September 2012; Stahl and Wermuth (2002) Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH; and Berge et al. (1977) Journal of Pharmaceutical Science, 66: 1-19, each of which is incorporated herein by reference in its entirety.

[0102] As used herein, the term “systemic inflammatory response syndrome” or “SIRS” refers to a clinical response arising from a non-specific insult with two or more of the following measureable clinical characteristics; a body temperature greater than 38°C or less than 36°C, a heart rate greater than 90 beats per minute, a respiratory rate greater than 20 per minute, a white blood cell count (total leukocytes) greater than 12,000 per mm3or less than 4,000 per mm3, or a band neutrophil percentage greater than 10%. From an immunological perspective, it may be seen as representing a systemic response to an infectious (e.g. pathogenic microbe) or non-infectious insult (e.g. major surgery) or systemic inflammation. Confirmation of infection can be determined using any suitable procedure known in the art, illustrative examples of whichinclude blood culture, nucleic acid detection (e.g. PCR, mass spectroscopy, immunological detection (e.g. ELISA), isolation of bacteria from infected cells, cell lysis and imaging techniques such as electron microscopy.

[0103] As used herein, the terms “treatment”, “treating”, and the like, refer to obtaining a desired pharmacologic and / or physiologic effect. The effect may be therapeutic in terms of a partial or complete cure for a disease or condition (e.g. a viral infection) and / or adverse effect attributable to the disease or condition. These terms also cover any treatment of a condition or disease in a subject, particularly in a human, and include: (a) inhibiting the disease or condition, i.e. arresting its development; or (b) relieving the disease or condition, i.e. causing regression of the disease or condition.

[0104] Each embodiment described herein is to be applied mutatis mutandis to each and every embodiment unless specifically stated otherwise. 2. Compounds

[0105] The present invention is predicated in part on the discovery of particular compounds that bind to the fusion protein of viruses and inhibit the interaction between the fusion protein and the host cell. Accordingly, the Inventors have conceived that such compounds will be useful for treating and inhibiting the development of a viral infection in a subject, especially an infection by a virus expressing a viral fusion protein, such as an enveloped virus infection (e.g. a coronavirus infection, such as a SARS-CoV-2 infection) or for treating conditions associated with viral infections, such as an acute inflammatory condition, CRS or a cytokine storm, or SARS.

[0106] Accordingly, one aspect of the invention provides a compound of Formula I, II or III:wherein: L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L2, L5and L14are independently selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X1, X2, X3, X4, X5, X6, X7, X8, X9, X10and X11are independently selected from CH and N; and R1is selected from optionally substituted C2-C12 alkyl, optionally substituted C2-C12 alkenyl and optionally substituted C2-C12 alkynyl.

[0107] Suitable optional substituents include, but are not limited to, methyl, ethyl and halogen. In particular embodiments, each optionally substituted alkylene, alkenylene, alkynylene, alkyl, alkenyl or alkynyl group may be substituted with 1-3 substituents, especially 1-3 methyl groups. In some embodiments, the alkylene, alkenylene, alkynylene, alkyl, alkenyl and alkynyl groups are unsubstituted.

[0108] In particular embodiments, X1-X11are CH. For the avoidance of any doubt, when X1-X11are CH, the carbon atom is a member of the ring (i.e. the ring is a triazole).

[0109] In some embodiments, L1is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3alkenylene and optionally substituted C2-C3alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0110] In some embodiments, L2is selected from optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; especially optionally substituted C2-C5 alkylene; more especially C2-C5 alkylene; most especially propylene (e.g. n-propylene).

[0111] In some embodiments, L3is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0112] In particular embodiments, L4is selected from optionally substituted C1- C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0113] In some embodiments, L5is selected from optionally substituted C3-C6 alkylene, optionally substituted C3-C6 alkenylene and optionally substituted C6-C6 alkynylene; especially optionally substituted C3-C6 alkylene; more especially C3-C6 alkylene; most especially butylene (e.g. n-butylene).

[0114] In particular embodiments, L6is selected from optionally substituted C1- C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3alkylene; more especially C1-C3alkylene; most especially methylene.

[0115] In specific embodiments, L7is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0116] In some embodiments, L8is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0117] In some embodiments, L9is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0118] In particular embodiments, L10is selected from optionally substituted C1-C3alkylene, optionally substituted C2-C3alkenylene and optionally substituted C2-C3alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0119] In some embodiments, L11is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0120] In some embodiments, L12is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0121] In some embodiments, L13is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0122] In some embodiments, L14is selected from optionally substituted C2-C4 alkylene, optionally substituted C2-C4 alkenylene and optionally substituted C2-C4 alkynylene; especially optionally substituted C2-C4 alkylene; more especially C2-C4 alkylene; most especially ethylene.

[0123] In some embodiments, L15is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3alkylene; more especially C1-C3alkylene; most especially methylene.

[0124] In some embodiments, L16is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0125] In some embodiments, L17is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0126] In some embodiments, L18is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3alkylene; more especially C1-C3alkylene; most especially methylene.

[0127] In some embodiments, L19is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; especially optionally substituted C1-C3 alkylene; more especially C1-C3 alkylene; most especially methylene.

[0128] In some embodiments, R1is selected from optionally substituted C6-C10 alkyl, optionally substituted C6-C10 alkenyl and optionally substituted C6-C10 alkynyl; especially optionally substituted C6-C10 alkyl; more especially C6-C10 alkyl. In particular embodiments, R1is selected from optionally substituted C7-C9 alkyl, optionally substituted C7-C9 alkenyl and optionally substituted C7-C9 alkynyl; especially optionally substituted C7-C9 alkyl; more especially C7-C9 alkyl; most especially octyl.

[0129] In specific embodiments, the compound is a compound of Formula I: or awherein: L1and L3are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L2is selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; and X1and X2are independently selected from CH and N.

[0130] Suitable embodiments of each of L1, L2, L3, X1and X2are discussed supra.

[0131] In particular embodiments: L1is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L2is selected from optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L3is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; and X1and X2are independently selected from CH and N.

[0132] In further embodiments: L1is optionally substituted C1-C3 alkylene; L2is optionally substituted C2-C5 alkylene; L3is optionally substituted C1-C3 alkylene; and X1and X2are independently selected from CH and N.

[0133] In particular embodiments: L1is methylene; L2is propylene (e.g. n-propylene); L3is methylene; and X1and X2are CH.

[0134] In specific embodiments, the compound of Formula I is a compound of Formula IV:

[0135] In specific embodiments, the compound is a compound of Formula II:wherein: L4, L6, L7and L8are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L5is selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X3, X4and X5are independently selected from CH and N; and R1is selected from optionally substituted C2-C12alkyl, optionally substituted C2-C12alkenyl and optionally substituted C2-C12 alkynyl.

[0136] Suitable embodiments of each of L4, L5, L6, L7, L8, X3, X4, X5and R1are discussed supra.

[0137] In particular embodiments: L4is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L5is selected from optionally substituted C3-C6 alkylene, optionally substituted C3-C6 alkenylene and optionally substituted C6-C6 alkynylene; L6is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L7is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L8is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; X3, X4and X5are independently selected from CH and N; andR1is selected from optionally substituted C6-C10 alkyl, optionally substituted C6-C10 alkenyl and optionally substituted C6-C10 alkynyl.

[0138] In particular embodiments: L4is optionally substituted C1-C3 alkylene; L5is optionally substituted C3-C6 alkylene; L6is optionally substituted C1-C3 alkylene; L7is optionally substituted C1-C3 alkylene; L8is optionally substituted C1-C3 alkylene; X3, X4and X5are independently selected from CH and N; and R1is optionally substituted C6-C10 alkyl.

[0139] In particular embodiments: L4is methylene; L5is butylene (e.g. n-butylene); L6is methylene; L7is methylene; L8is methylene; X3, X4and X5are CH; and R1is C7-C9 alkyl, especially octyl.

[0140] In particular embodiments, the compound of Formula II is a compound of Formula V:

[0141] In alternative embodiments, the compound is a compound of Formula III:wherein: L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L14is selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; and X6, X7, X8, X9, X10and X11are independently selected from CH and N.

[0142] Suitable embodiments of each of L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, X6, X7, X8, X9, X10and X11are discussed supra.

[0143] In particular embodiments: L9is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L10is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L11is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L12is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L13is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene;L14is selected from optionally substituted C2-C4 alkylene, optionally substituted C2-C4 alkenylene and optionally substituted C2-C4 alkynylene; L15is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L16is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L17is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L18is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; L19is selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene; and X6, X7, X8, X9, X10and X11are independently selected from CH and N.

[0144] In specific embodiments: L9is optionally substituted C1-C3 alkylene; L10is optionally substituted C1-C3 alkylene; L11is optionally substituted C1-C3 alkylene; L12is optionally substituted C1-C3 alkylene; L13is optionally substituted C1-C3 alkylene; L14is optionally substituted C2-C4 alkylene; L15is optionally substituted C1-C3 alkylene; L16is optionally substituted C1-C3 alkylene; L17is optionally substituted C1-C3 alkylene; L18is optionally substituted C1-C3 alkylene; L19is optionally substituted C1-C3 alkylene; and X6, X7, X8, X9, X10and X11are independently selected from CH and N.

[0145] In some embodiments: L9is methylene; L10is methylene; L11is methylene;L12is methylene; L13is methylene; L14is ethylene; L15is methylene; L16is methylene; L17is methylene; methylene; L19is methylene; and X6, X7, X8, X9, X10and X11are CH.

[0146] In some embodiments, the compound of Formula III is a compound of Formula VI:

[0147] In particular embodiments, the invention provides a compound of Formula I, II, III, IV, V or VI, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0148] Provided herein is a compound of Formula I or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0149] Further provided herein is a compound of Formula II or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula II or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0150] In another aspect, there is provided a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula III or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0151] As discussed above, the invention provides a compound of Formula IV or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula IV or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0152] Further provided herein is a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula V or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0153] In another aspect, there is provided a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the invention provides a compound of Formula VI or a pharmaceutically acceptable salt thereof. In some embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt.

[0154] Also disclosed herein in the methods of the invention is a compound of Formula VII:

[0155] In some embodiments, the compound of Formula VII is in the form of a pharmaceutically acceptable salt, such as a potassium, lithium or sodium salt, especially the sodium salt.

[0156] In some embodiments, the compound of the invention is G4, G19, G22 or G24; especially G19, G22 or G24; most especially G24.

[0157] The compounds of the invention may also be in the form of pharmaceutically acceptable salts, solvates or prodrugs. In some embodiments, the compounds may be in the form of hydrates.

[0158] While any suitable salt is contemplated, in some embodiments, compounds of the invention are in the form of a pharmaceutically acceptable salt. In particular embodiments, the salt is the potassium, lithium or sodium salt, especially the sodium salt. A skilled person will be well aware of methods for preparing suitable salts of the compounds of the invention.

[0159] In some embodiments, the prodrug is an ester, such as O-neopentyl ester (e.g. as described in Gordon et al. (2018) J Med Chem, 61: 10340-10344, the entire content of which is incorporated herein by reference).

[0160] The compounds may be prepared using techniques known in the art, such as the methods disclosed in WO 2018 / 068090 A1, the entire contents of which are incorporated herein by reference. 3. Compositions

[0161] While it is possible that the compounds of the invention may be administered in an undiluted form, it is preferable to present such compounds in the form of a pharmaceutical composition. Thus, in some embodiments, the compounds may be in the form of a pharmaceutical composition, wherein the pharmaceutical composition comprises a compound of the invention and a pharmaceutically acceptable carrier or diluent.

[0162] The compound may be formulated into the pharmaceutical composition as a neutral or salt form, especially as a sodium salt.

[0163] As will be appreciated by those skilled in the art, the choice of pharmaceutically acceptable carrier or diluent will be dependent on the route of administration and on the nature of the condition and subject to be treated. The particular carrier or delivery system and route of administration may be readily determined by a person skilled in the art. The carrier or delivery system and route of administration should be carefully selected to ensure that the activity of the compound is not depleted during preparation of the formulation and the compound is able to reach the site of action intact. The pharmaceutical compositions of the invention may be administered through a variety of routes including, but not limited to, oral, rectal, topical, intranasal, inhalation, intraocular, transmucosal, intestinal, enteral, intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular, intracerebral, intravaginal, intravesical, intravenous or intraperitoneal administration. In particular embodiments, the pharmaceutical composition is administered via oral, inhalation, intranasal, topical or intravenous administration; especially oral, inhalation or intranasal administration.

[0164] The pharmaceutical forms suitable for injectable use include sterile injectable solutions or dispersions and sterile powders for the preparation of sterileinjectable solutions. Such forms should be stable under the conditions of manufacture and storage and may be preserved against reduction, oxidation and microbial contamination.

[0165] A person skilled in the art will readily be able to determine appropriate formulations for the compounds using conventional approaches. Techniques for formulation and administration may be found in, for example, Remington: The Science and Practice of Pharmacy, Loyd V. Allen, Jr (Ed), The Pharmaceutical Press, London, 22ndEdition, September 2012.

[0166] Identification of preferred pH ranges and suitable excipients, such as antioxidants, is routine in the art, for example, as described in Katdare and Chaubel (2006) Excipient Development for Pharmaceutical, Biotechnology and Drug Delivery Systems (CRC Press). Buffer systems are routinely used to provide pH values of a desired range and may include, but are not limited to, carboxylic acid buffers, such as acetate, citrate, lactate, tartrate and succinate; glycine; histidine; phosphate; tris(hydroxymethyl)aminomethane (Tris); arginine; sodium hydroxide; glutamate; and carbonate buffers. Suitable antioxidants may include, but are not limited to, phenolic compounds such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole; vitamin E; ascorbic acid; reducing agents such as methionine or sulphite; metal chelators such as ethylene diamine tetraacetic acid (EDTA); cysteine hydrochloride; sodium bisulfite; sodium metabisulfite; sodium sulfite; ascorbyl palmitate; lecithin; propyl gallate; and alpha-tocopherol.

[0167] For injection, the compound may be formulated in an aqueous solution, suitably in physiologically compatible buffers such as Hanks’ solution, Ringer’s solution, dextrose solution or physiological saline buffer, such as phosphate buffered saline (PBS). For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

[0168] The compositions of the present invention may be formulated for administration in the form of liquids, containing acceptable diluents (such as saline and sterile water), or may be in the form of lotions, creams or gels containing acceptable diluents or carriers to impart the desired texture, consistency, viscosity and appearance. Acceptable diluents and carriers are familiar to those skilled in the art and include, but are not restricted to, ethoxylated and nonethoxylated surfactants, fatty alcohols, fatty acids, hydrocarbon oils (such as palm oil, coconut oil, and mineral oil), cocoa butter waxes, silicon oils, pH balancers, cellulose derivatives, emulsifying agents such as non- ionic organic and inorganic bases, preserving agents, wax esters, steroid alcohols, triglyceride esters, phospholipids such as lecithin and cephalin, polyhydric alcohol esters, fatty alcohol esters, hydrophilic lanolin derivatives and hydrophilic beeswax derivatives.

[0169] Alternatively, the compound can be formulated readily using pharmaceutically acceptable carriers well known in the art into dosages suitable for oral administration, which is also contemplated for the practice of the invention. Such carriers enable the compounds of the invention to be formulated in dosage forms such as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. These carriers may be selected from sugars, chitosan, starches, cellulose and its derivatives, malt, gelatin, talc, calcium sulfate, vegetable oils, synthetic oils, polyols, alginic acid, phosphate buffered solutions, emulsifiers, isotonic saline and pyrogen-free water.

[0170] Pharmaceutical formulations for parenteral administration include aqueous solutions of the composition in water-soluble form. Additionally, suspensions of the compound may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran. Optionally, the suspension may also contain suitable stabilizers or agents that increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.

[0171] Sterile solutions may be prepared by combining the compound in the required amount in the appropriate solvent with other excipients as described above as required, followed by sterilization, such as filtration. Generally, dispersions are prepared by incorporating the various sterilized active compounds into a sterile vehicle which contains the basic dispersion medium and the required excipients as described above. Sterile dry powders may be prepared by vacuum- or freeze-drying a sterile solution comprising the active compounds and other required excipients as described above.

[0172] Pharmaceutical preparations for oral use can be obtained by combining the compounds with solid excipients and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatine, gum tragacanth, methyl cellulose, hydroxypropylmethyl- cellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate. Such compositions may be prepared by any of the methods of pharmacy but all methods include the step of bringing into association one or more therapeutic agents as described above with the carrier which constitutes one or more necessary ingredients. In general, the pharmaceuticalcompositions of the present invention may be manufactured in a manner that is itself known, e.g. by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.

[0173] Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of particle doses.

[0174] Pharmaceuticals which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added.

[0175] The compounds may be incorporated into modified-release preparations and formulations, for example, polymeric microsphere formulations, and oil- or gel-based formulations.

[0176] The compounds may be administered in a local rather than systemic manner, such as by injection directly into a tissue, which is preferably subcutaneous or omental tissue, often in a depot or sustained release formulation. In other embodiments, the compound is systemically administered.

[0177] Furthermore, the compound may be administered in a targeted drug delivery system, such as in a particle which is suitable targeted to and taken up selectively by a cell or tissue. In some embodiments, the compound is contained or otherwise associated with a vehicle selected from liposomes, micelles, dendrimers, biodegradable particles, artificial DNA nanostructure, lipid-based nanoparticles and carbon or old nanoparticles. In illustrative examples of this type, the vehicle is selected from poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) (PEG), PLA-PEG copolymers and combinations thereof.

[0178] In cases of local administration or selective uptake, the effective local concentration of the agent may not be related to plasma concentration.

[0179] In some embodiments, the compositions are suitable for inhalation or intranasal delivery and are in the form of, for example, solutions, aerosols, dry powders, suspensions or emulsions. For example, the composition may be administered to therespiratory tract as a nasal or pulmonary inhalation aerosol or solution for a nebulizer, or as a microfine powder (e.g. with particles in the order of 1 to 10 μm in diameter or less) for insufflation, alone or in combination with an inert carrier, such as lactose or glucose, or with other pharmaceutically acceptable excipients, such as beta-cyclodextrin, starch, sodium carboxymethylcellulose and the like.

[0180] Aerosol formulations include those in which the compound is provided in a pressurised pack with a suitable propellant such as a metered dose inhaler. Whilst the propellant may be a chlorofluorocarbon (CFC) (such as dichlorodifluoromethane, trichlorofluoromethane or 1,2-dichlorotetrafluoroethane), the propellant is more preferably a non-chlorofluorocarbon propellant such as an inert gas (e.g. carbon dioxide, nitrogen or nitrogen dioxide), a hydrofluoroalkane [e.g. 1,1,1,2-tetrafluoroethane (HFA- 134a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227), 1,1-difluoroethane (HFC-152a) or 1,1,1,2,3,3,3-heptafluoroethane (HFA-227ea)], hydrochlorofluorocarbon, hydrofluoroolefin [e.g. 1,3,3,3-tetrafluoroprop-1-ene (HFO-1234ze) or 2,3,3,3- tetrafluoroprop-1-ene (HFO-1234yf)] or compressed gas (e.g. compressed air). The aerosol may conveniently also contain a surfactant such as lecithin. The dose of the compound may be controlled by provision of a metered valve. It has been found that a particle size of approximately 1 to 5 μm is useful for delivery to the lung, as particles smaller than 1 μm are generally exhaled without delivery to the lung, and particles larger than 10 μm are mostly trapped by oropharyngeal deposition and do not reach the lung. Devices propelled by HFA-134a deliver smaller droplets which penetrate more readily into the bronchial airways. For drug delivery via the nasal passage, a suitable particle size is, for example, 20-80 μm, as smaller particles (less than 10 μm) get carried into the tracheobrachial region, whilst bigger particles (greater than 100 μm) get rapidly cleared from the nasal passageway.

[0181] The compound may also be provided in a pharmaceutical formulation which forms a gel in the nasal cavity. The compound may also be formulated in a powder composition which may be presented in unit dose form for example in capsules or cartridges of e.g. gelatin, or blister packs from which the powder may be administered by means of an inhaler.

[0182] It is advantageous to formulate the compositions in dosage unit form for ease of administration and uniformity of dosage. The determination of the novel dosage unit forms of the present invention is dictated by and directly dependent on the unique characteristics of the active material, the particular therapeutic effect to be achieved and the limitations inherent in the art of compounding active materials for the treatment of disease in living subjects having a diseased condition in which bodily health is impaired as herein disclosed in detail.

[0183] While the compound of the invention may be the sole active agent administered to the subject, the administration of other active agents concurrently with said compound is within the scope of the invention. For example, in some embodiments, the compound may be administered concurrently with one or more antimicrobial agents, anti-inflammatory agents, or agents which inhibit the cytokine storm. The compound may be therapeutically used after the other active agent or may be therapeutically used together with the other active agent. The compound may be administered separately, simultaneously or sequentially with the other active agent.

[0184] Accordingly, in another aspect of the invention, there is provided a composition comprising a compound of the invention (such as a compound of Formula I, II, III, IV, V, VI or VII) and an antimicrobial agent, an anti-inflammatory agent or an agent which inhibits the cytokine storm.

[0185] Suitable antimicrobial agents include without limitation compounds that kill or inhibit the growth of microorganisms such as viruses, bacteria, yeast, fungi, protozoa, etc. and thus include antibiotics, antifungals, antiprotozoals, antimalarials, antituberculotics and antivirals. In particular embodiments, the antimicrobial agent is an antiviral.

[0186] Illustrative antibiotics include quinolones (e.g. amifloxacin, cinoxacin, ciprofloxacin, enoxacin, fleroxacin, flumequine, lomefloxacin, nalidixic acid, norfloxacin, ofloxacin, levofloxacin, lomefloxacin, oxolinic acid, pefloxacin, rosoxacin, temafloxacin, tosufloxacin, sparfloxacin, clinafloxacin, gatifloxacin, moxifloxacin; gemifloxacin; and garenoxacin), tetracyclines, glycylcyclines and oxazolidinones (e.g. chlortetracycline, demeclocycline, doxycycline, lymecycline, methacycline, minocycline, oxytetracycline, tetracycline, tigecycline; linezolide, eperozolid), glycopeptides, aminoglycosides (e.g. amikacin, arbekacin, butirosin, dibekacin, fortimicins, gentamicin, kanamycin, meomycin, netilmicin, ribostamycin, sisomicin, spectinomycin, streptomycin, tobramycin), ^-lactams (e.g. imipenem, meropenem, biapenem, cefaclor, cefadroxil, cefamandole, cefatrizine, cefazedone, cefazolin, cefixime, cefmenoxime, cefodizime, cefonicid, cefoperazone, ceforanide, cefotaxime, cefotiam, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, ceftazidime, cefteram, ceftezole, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, cefuzonam, cephaacetrile, cephalexin, cephaloglycin, cephaloridine, cephalothin, cephapirin, cephradine, cefinetazole, cefoxitin, cefotetan, azthreonam, carumonam, flomoxef, moxalactam, amidinocillin, amoxicillin, ampicillin, azlocillin, carbenicillin, benzylpenicillin, carfecillin, cloxacillin, dicloxacillin, methicillin, mezlocillin, nafcillin, oxacillin, penicillin G, piperacillin, sulbenicillin, temocillin, ticarcillin, cefditoren, SC004, KY-020, cefdinir, ceftibuten, FK-312, S-1090, CP-0467, BK-218, FK-037, DQ-2556, FK- 518, cefozopran, ME1228, KP-736, CP-6232, Ro 09-1227, OPC-20000, LY206763),rifamycins, macrolides (e.g. azithromycin, clarithromycin, erythromycin, oleandomycin, rokitamycin, rosaramicin, roxithromycin, troleandomycin), ketolides (e.g. telithromycin, cethromycin), coumermycins, lincosamides (e.g. clindamycin, lincomycin) and chloramphenicol. Representative antivirals include abacavir sulfate, acyclovir sodium, amantadine hydrochloride, amprenavir, cidofovir, delavirdine mesylate, didanosine, efavirenz, famciclovir, fomivirsen sodium, foscarnet sodium, ganciclovir, indinavir sulfate, lamivudine, lamivudine / zidovudine, nelfinavir mesylate, nevirapine, oseltamivir phosphate, ribavirin, rimantadine hydrochloride, ritonavir, saquinavir, saquinavir mesylate, stavudine, valacyclovir hydrochloride, valganciclovir, zalcitabine, zanamivir, and zidovudine. Non-limiting examples of antiprotozoals include atovaquone, chloroquine hydrochloride, chloroquine phosphate, metronidazole, metronidazole hydrochloride, and pentamidine isethionate. Suitable anthelmintics can be at least one selected from mebendazole, pyrantel pamoate, albendazole, ivermectin and thiabendazole. Illustrative antifungals can be selected from amphotericin B, amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposomal, bifonazole, butoconazole, chlordantoin, chlorphenesin, ciclopirox olamine, clotrimazole, eberconazole, econazole, fluconazole, flucytosine, flutrimazole, griseofulvin microsize, griseofulvin ultramicrosize, itraconazole, isoconazole, itraconazole, ketoconazole, miconazole, nifuroxime, nystatin, terbinafine hydrochloride, tioconazole, terconazole and undecenoic acid. Non-limiting examples of antimalarials include chloroquine hydrochloride, chloroquine phosphate, doxycycline, hydroxychloroquine sulfate, mefloquine hydrochloride, primaquine phosphate, pyrimethamine, and pyrimethamine with sulfadoxine. Antituberculotics include, but are not restricted to, clofazimine, cycloserine, dapsone, ethambutol hydrochloride, isoniazid, pyrazinamide, rifabutin, rifampin, rifapentine, and streptomycin sulfate.

[0187] In some embodiments, the ancillary active agent is an anti-inflammatory agent, representative examples of which include steroidal anti-inflammatory agents such as but not limited to compounds containing a 17-carbon 4-ring system, including sterols, various hormones (as anabolic steroids), and glycosides. Representative examples of steroidal anti-inflammatory drugs include, without limitation, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone- phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone,fludrocortisone, diflorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, and mixtures thereof.

[0188] Alternatively, the anti-inflammatory agent may be a nonsteroidal anti- inflammatory agent, non-limiting examples of which include agents that are aspirin-like in their action, including, but not limited to, ibuprofen (ADVIL), naproxen sodium (ALEVE), and acetaminophen (TYLENOL). Additional examples of non-steroidal anti- inflammatory agents include, without limitation, oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP-14,304; disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac; fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic, and tolfenamic acids; propionic acid derivatives, such as benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic; pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, azapropazone, and trimethazone. Mixtures of these non- steroidal anti-inflammatory agents also may be employed, as well as the dermatologically acceptable salts and esters of these agents. For example, etofenamate, a flufenamic acid derivative, is particularly useful for topical application.

[0189] In other embodiments, the anti-inflammatory agent includes, without limitation, transforming growth factor-beta 3 (TGF-β3), an anti-tumor necrosis factor- alpha (TNF-α) agent, an inhibitor or antagonist of IL-6 or IL-6 receptor, IL-1 receptor, IL- 1β, TNF, GM-CSF, IFN-γ, JAK-STAT signaling, CCR2, CCR5, complement component C5, IRAK4 and M-CSF receptor, or a combination thereof.

[0190] The compounds of the invention may also be administered concurrently with agents which inhibit the cytokine storm. For example, suitable agents include compounds that target fundamental immune pathways, such as the chemokine network and the cholinergic anti-inflammatory pathway. For example, JAK inhibitors, such as JAK 1 and JAK 2 inhibitors, can inhibit the cytokine storm, and in some cases, are also antiviral. Representative JAK inhibitors include those disclosed in U.S. Pat. No. 10,022,378, such as Jakafi, Tofacitinib, and Baricitinib, as well as LY3009104 / INCB28050, Pacritinib / SB1518, VX-509, GLPG0634, INC424, R-348, CYT387,TG 10138, AEG 3482, and pharmaceutically acceptable salts and prodrugs thereof. Still further examples include CEP-701 (Lestaurtinib), AZD1480, INC424, R-348, CYT387, TG 10138, AEG 3482, 7-iodo-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(4- aminophenyl)-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, N-(4-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl) acrylamide, 7-(3- aminophenyl)-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, N-(3-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl) acrylamide, N-(4- morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, methyl 2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidine-7-carboxylate, N-(4-morpholinophenyl)- 5H-pyrrolo[3,2-d]pyrimidin-2-amine, 7-(4-amino-3-methoxyphenyl)-N-(4- morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 4-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, N,N-dimethyl- 3-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, 1- ethyl-3-(2-methoxy-4-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin- -7- yl)phenyl)urea, N-(4-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7- yl)phenyl)methanesulfonamide, 2-methoxy-4-(2-(4-morpholinophenylamino)thieno[3,2- d]pyrimidin-7-yl)phenol, 2-cyano-N-(3-(2-(4-morpholinophenylamino)thieno[3,2- d]pyrimidin-7-yl)phenyl)acetamide, N-(cyanomethyl)-2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidine-7-carboxamide, N-(3-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanesulfonamide, 1- ethyl-3-(4-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)-2- (trifluoromethoxy)phenyl)urea, N-(3-nitrophenyl)-7-phenylthieno[3,2-d]pyrimidin-2- amine, 7-iodo-N-(3-nitrophenyl)thieno[3,2-d]pyrimidin-2-amine, N1-(7-(2- ethylphenyl)thieno[3,2-d]pyrimidin-2-yl)benzene-1,3-diamine, N-tert-butyl-3-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, N1-(7- iodothieno[3,2-d]pyrimidin-2-yl)benzene-1,3-diamine, 7-(4-amino-3- (trifluoromethoxy)phenyl)-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(2- ethylphenyl)-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, N-(3-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetamide, N- (cyanomethyl)-N-(3-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7- yl)phenyl)methanesulfonamide, N-(cyanomethyl)-N-(4-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanesulfonamide, N-(3- (5-methyl-2-(4-morpholinophenylamino)-5H-pyrrolo[3,2-d]pyrimidin-7- yl)phenyl)methanesulfonamide, 4-(5-methyl-2-(4-morpholinophenylamino)-5H- pyrrolo[3,2-d]pyrimidin-7-yl)benzenesulfonamide, N-(4-(5-methyl-2-(4- morpholinophenylamino)-5H-pyrrolo[3,2-d]pyrimidin-7-yl)phenyl)methanesulfonamide, 7-iodo-N-(4-morpholinophenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-amine, 7-(2- isopropylphenyl)-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 7-bromo-N-(4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, N7-(2-isopropylphenyl)-N2-(4- morpholinophenyl)thieno[3,2-d]pyrimidine-2,7-diamine, N7-(4-isopropylphenyl)-N2-(4- morpholinophenyl)thieno[3,2-d]pyrimidine-2,7-diamine, 7-(5-amino-2-methylphenyl)-N- (4-morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, N-(cyanomethyl)-4-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)benzamide, 7-iodo-N-(3- morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(4-amino-3-nitrophenyl)-N-(4- morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(2-methoxypyridin-3-yl)-N-(4- morpholinophenyl)thieno[3,2-d]pyrimidin-2-amine, (3-(7-iodothieno[3,2-d]pyrimidin-2- ylamino)phenyl)methanol, N-tert-butyl-3-(2-(3-morpholinophenylamino)thieno[3,2- d]pyrimidin-7-yl)benzenesulfonamide, N-tert-butyl-3-(2-(3- (hydroxymethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, N-(4- morpholinophenyl)-7-(4-nitrophenylthio)-5H-pyrrolo[3,2-d]pyrimidin-2-amine, N-tert- butyl-3-(2-(3,4,5-trimethoxyphenylamino)thieno[3,2-d]pyrimidin-7- yl)benzenesulfonamide, 7-(4-amino-3-nitrophenyl)-N-(3,4-dimethoxyphenyl)thieno[3,2- d]pyrimidin-2-amine, N-(3,4-dimethoxyphenyl)-7-(2-methoxypyridin-3-yl)thieno[3,2- d]pyrimidin-2-amine, N-tert-butyl-3-(2-(3,4-dimethoxyphenylamino)thieno[3,2- d]pyrimidin-7-yl)benzenesulfonamide, 7-(2-aminopyrimidin-5-yl)-N-(3,4- dimethoxyphenyl)thieno[3,2-d]pyrimidin-2-amine, N-(3,4-dimethoxyphenyl)-7-(2,6- dimethoxypyridin-3-yl)thieno[3,2-d]-pyrimidin-2-amine, N-(3,4-dimethoxyphenyl)-7- (2,4-dimethoxypyrimidin-5-yl)thieno[3,2-d]pyrimidin-2-amine, 7-iodo-N-(4- (morpholinomethyl)phenyl)thieno[3,2-d]pyrimidin-2-amine, N-tert-butyl-3-(2-(4- (morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, 2- cyano-N-(4-methyl-3-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7- yl)phenyl)acetamide, ethyl 3-(2-(4-morpholinophenylamino)thieno[3,2-d]pyrimidin-7- yl)benzoate, 7-bromo-N-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidin-2- amine, N-(3-(2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)thieno[3,2-d]pyrimidin-7- yl)phenyl)acetamide, N-(cyanomethyl)-3-(2-(4-morpholinophenylamino)thieno[3,2- d]pyrimidin-7-yl)benzamide, N-tert-butyl-3-(2-(4-morpholinophenylamino)thieno[3,2- d]pyrimidin-7-yl)benzamide, N-tert-butyl-3-(2-(4-(1-ethylpiperidin-4- yloxy)phenylamino)thieno-[3,2-d]pyrimidin-7-yl)benzenesulfonamide, tert-butyl-4-(2-(4- (morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)-1H-pyrazole-1- carboxylate, 7-bromo-N-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)thieno[3,2- d]pyrimidin-2-amine, N-tert-butyl-3-(2-(4-((4-ethylpiperazin-1-yl)methyl)phenylamino)- -thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, N-(4-((4-ethylpiperazin-1- yl)methyl)phenyl)-7-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-amine, N-(cyanomethyl)- 3-(2-(4-(morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzamide, N-tert- butyl-3-(2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)thieno[3,2-d]-pyrimidin-7- yl)benzenesulfonamide, tert-butyl pyrrolidin-1-yl)ethoxy)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzylcarbamate, 3-(2-(4-(2-(pyrrolidin-1- yl)ethoxy)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzenesulfonamide, 7-(3-chloro-4- fluorophenyl)-N-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)thieno-[3,2-d]pyrimidin-2-amine, tert-butyl 4-(2-(4-(1-ethylpiperidin-4-yloxy)phenylamino)thieno[3,2-d]pyrimidin-7-yl)- 1H-pyrazole-1-carboxylate, 7(benzo[d][1,3]dioxol-5-yl)-N-(4- (morpholinomethyl)phenyl)thieno[3,2-d]pyrimidin-2-amine, tert-butyl 5-(2-(4- (morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)-1H-indole-1-carboxylate, 7-(2-aminopyrimidin-5-yl)-N-(4-(morpholinomethyl)phenyl)thieno[3,2-d]pyrimidin-2- amine, tert-butyl 4-(2-(-4-(morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)- 5,6-di-hydropyridine-1(2H)-carboxylate, tert-butyl morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzylcarbamate, N-(3-(2- (4-(morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetamide, N-(4- (2-(4-(morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetamide, N- (3-(2-(4-(morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7- yl)phenyl)methanesulfonamide, 7-(4-(4-methylpiperazin-1-yl)phenyl)-N-(4- (morpholinomethyl)phenyl)thieno-[3,2-d]pyrimidin-2-amine, N-(2-methoxy-4-(2-(4- (morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetamide, 7- bromo-N-(3,4,5-trimethoxyphenyl)thieno[3,2-d]pyrimidin-2-amine, (3-(2-(3,4,5- trimethoxyphenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanol, (4-(2-(3,4,5- trimethoxyphenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanol, (3-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanol, (4-(2-(4- morpholinophenylamino)thieno[3,2-d]pyrimidin-7-yl)phenyl)methanol, N-(pyrrolidin-1- yl)ethoxy)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzyl)methanesulfonamide, tert- butyl morpholinomethyl)phenylamino)thieno[3,2-d]pyrimidin-7-yl)benzylcarbamate, N- (4-(morpholinomethyl)phenyl)-7-(3-(piperazin-1-yl)phenyl)thieno[3,2-d]pyrimidin-2- amine, 7-(6-(2-morpholinoethylamino)pyridin-3-yl)-N-(3,4,5- trimethoxyphenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(2-ethylphenyl)-N-(4-(2- (pyrrolidin-1-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidin-2-amine, 7-(4- (aminomethyl)phenyl)-N-(4-(morpholinomethyl)phenyl)thieno[3,2-d]pyrimidin-2-amine, N-(4-(1-ethylpiperidin-4-yloxy)phenyl)-7-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2- amine, N-(2,4-dimethoxyphenyl)-7-phenylthieno[3,2-d]pyrimidin-2-amine, 7-bromo-N- (3,4-dimethoxyphenyl)thieno[3,2-d]pyrimidin-2-amine, N-(3,4-dimethoxyphenyl)-7- phenylthieno[3,2-d]pyrimidin-2-amine, and pharmaceutically acceptable salts and prodrugs thereof.

[0191] Alternatively, or in addition, HMGB1 antibodies and / or COX-2 inhibitors can be used, which downregulate the cytokine storm. Examples of such compounds include Actemra (Roche). Celebrex (celecoxib), a COX-2 inhibitor, can be used. IL-8 (CXCL8) inhibitors can also be used.

[0192] As previously described, the compound may be compounded for convenient and effective administration in effective amounts with a suitable pharmaceutically acceptable carrier in dosage unit form. Suitable unit dosages and maximum daily dosages of the compound of the invention may be determined in accordance with the unit doses and maximum daily doses used conventionally. In some embodiments, a unit dosage form may comprise the compound in an amount in the range of from about 0.25 μg to about 2000 mg. The compound may be present in an amount of from about 0.25 μg to about 2000 mg / mL of carrier. In embodiments where the pharmaceutical composition comprises one or more additional active ingredients, the dosages are determined by reference to the usual dose and manner of administration of the said ingredients. 4. Methods of Use

[0193] The compounds of the invention have been found to interact with viral fusion proteins (e.g. the spike protein) and inhibit the interaction between the fusion protein and the host cell (e.g. ACE2 of the host cell). Accordingly, the Inventors have conceived that such compounds will be useful for treating and inhibiting the development of a viral infection in a subject, especially an infection by a virus expressing a viral fusion protein, such as an enveloped virus infection (e.g. a coronavirus infection, such as a SARS-CoV-2 infection) or for treating conditions associated with viral infections (e.g. coronavirus infections), such as an acute inflammatory condition, CRS or a cytokine storm, or SARS. Therefore, a compound of Formula I, II, III, IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in therapy is contemplated.

[0194] In another aspect, the invention provides a method of treating or inhibiting the development of a viral infection in a subject comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

[0195] Further provided is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating or inhibiting the development of a viral infection in a subject; use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating or inhibiting the development of a viral infection in a subject; and use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating or inhibiting the development of a viral infection in a subject.

[0196] Suitable embodiments of the compounds of Formulae I, II, III, IV, V, VI and VII are as discussed supra.

[0197] In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt thereof; especially a compound of Formula III or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of Formula I, II or III; especially a compound of Formula III.

[0198] In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of Formula IV, V or VI; especially a compound of Formula VI.

[0199] While the utility of the compounds for treating or inhibiting the development of any viral infection is contemplated, in particular embodiments, the virus is one which expressing a viral fusion protein. In some embodiments, the virus is an enveloped virus, especially an enveloped RNA virus, such as a flavivirus (e.g. dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, St. Louis encephalitis virus, tick-borne encephalitis virus, bovine viral diarrhea virus and classical swine fever virus), togavirus (e.g. sindbis virus, the equine encephalitis viruses, chikungunya virus, rubella virus, Ross River virus, bovine diarrhea virus, hog cholera virus and Semliki forest virus), coronavirus (e.g. betacoronaviruses such OC43 and HKU1 of the A lineage, swine gastroenteritis virus, a Severe Acute Respiratory Syndrome virus (SARS-CoV), Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) and Middle East Respiratory Syndrome virus (MERS)), orthomyxovirus (e.g. human influenza viruses, including human influenza virus types A, B and C, avian influenza viruses and equine influenza viruses), paramyxovirus (e.g. measles virus, canine distemper virus, mumps virus, parainfluenza viruses, respiratory syncytial virus, Newcastle disease virus, rinderpest virus, Nipah virus and Hendra virus), rhabdovirus (e.g. rabies virus, Australian bat lyssavirus and vesicular stomatitis viruses), bunyavirus (e.g. hantavirus, LaCrosse virus and Rift Valley fever virus) or filovirus (e.g. Marburg virus and Ebola virus); or an enveloped DNA virus, such as a herpesvirus (e.g. herpes simplex virus 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus), poxvirus (e.g. smallpox virus, vaccinia virus, cowpox virus, monkeypox virus, rabbitpox virus, orf virus, pseudocowpox, bovine papular stomatitis virus, tanapox virus, yaba monkey tumor virus, and molluscum contagiosum virus), hepadnavirus (e.g. hepatitis B virus), or asfarviridae (e.g. African swine fever virus).

[0200] In particular embodiments, the virus is a coronavirus, especially wherein the coronavirus is capable of causing severe acute respiratory syndrome (SARS). In some embodiments, the coronavirus is a betacoronavirus, such as one selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV.

[0201] In particular embodiments, the infection is caused by a virus that interacts with an ACE2 polypeptide-expressing cell, for example, when the virus contains a spike protein. In such embodiments, the virus is an ACE2-binding coronavirus. Suitable coronaviruses include a lineage B betacoronavirus, such as SARS-CoV or SARS- CoV-2.

[0202] The ACE2 polypeptide-expressing cell may be any cell expressing ACE2, such as a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell. In particular embodiments, the cell is a cell of the respiratory tract.

[0203] In another aspect, there is provided a method of inhibiting the interaction of a virus with an ACE2 polypeptide-expressing cell, comprising, consisting or consisting essentially of contacting the virus with a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof. Also provided is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in inhibiting the interaction of a virus with an ACE2 polypeptide-expressing cell; use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for inhibiting the interaction of a virus with an ACE2 polypeptide-expressing cell; and use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for inhibiting the interaction of a virus with an ACE2 polypeptide-expressing cell.

[0204] In some embodiments, the interaction is one or both of binding of the virus to the cell and entry of the virus into the cell; especially entry of the virus into the cell.

[0205] Suitable embodiments of the compounds of Formulae I, II, III, IV, V, VI and VII are as discussed supra.

[0206] In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt thereof; especially a compound of Formula III or a pharmaceutically acceptable salt thereof. In particular embodiments, the compound is a compound of Formula I, II or III; especially a compound of Formula III.

[0207] In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt thereof. In particular embodiments, the compound is a compound of Formula IV, V or VI; especially a compound of Formula VI.

[0208] The ACE2 polypeptide-expressing cell may be any cell expressing ACE2, such as a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell. In particular embodiments, the cell is a cell of the respiratory tract.

[0209] Suitable embodiments of the virus are as discussed supra. In particular embodiments, the virus is a coronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2.

[0210] In a further aspect, there is provided a method of treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. Also provided is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection; a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection; and a use of a compound of Formula I, II, III IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection.

[0211] Suitable embodiments of the compounds of Formulae I, II, III, IV, V, VI and VII are as discussed supra.

[0212] In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt thereof; especially a compound of Formula III or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of Formula I, II or III; especially a compound of Formula III.

[0213] In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt thereof. In particular embodiments, the compound is a compound of Formula IV, V or VI; especially a compound of Formula VI.

[0214] In particular embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV. In specific embodiments, the coronavirus is an ACE2-binding coronavirus, such as a lineage B betacoronavirus, including SARS-CoV or SARS-CoV-2.

[0215] In some embodiments, the acute inflammatory condition is associated with presence of cytokine release syndrome (CRS) or a cytokine storm. Illustrative examples of this type include wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0216] The acute inflammatory condition may be associated with the presence of CRS, in which the subject, for example, has one or more symptoms selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. The acute inflammatory condition may be associated with the presence of a cytokine storm and, for example, the subject may have one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof.

[0217] In some embodiments, the acute inflammatory condition is associated with a multisystem inflammatory syndrome in children (MIS-C) wherein the subject, for example, has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0218] The acute inflammatory condition may also be associated with a systemic inflammatory response syndrome (SIRS). The subject may have one or more symptoms associated with a particular stage of SIRS, representative ones of which are as follows:

[0219] Stage 1 is a local reaction at the site of injury that aims at containing the injury and limit spread. Immune effector cells at the site release cytokines that in turn stimulate the reticuloendothelial system promoting wound repair through local inflammation. There is local vasodilatation induced by nitric oxide and prostacyclin (rubor) and disruption of the endothelial tight junction to allow margination and transfer of leucocytes into tissue space. The leakage of cells and protein-rich fluid in extravascular space causes swelling (tumor) and increased heat (calor). Inflammatory mediators impact the local somatosensory nerves causing pain (dolor) and loss of function (functio laesa). That loss of function also allows the part of the body to repair instead of persistent use.

[0220] Stage 2 is an early compensatory anti-inflammatory response syndrome (CARS) in an attempt to maintain immunological balance. There is a stimulation of growth factors and recruitment of macrophages and platelets as the level of pro- inflammatory mediators decreases to maintain homeostasis.

[0221] Stage 3 is when the scale tips over towards pro-inflammatory SIRS resulting in progressive endothelial dysfunction, coagulopathy, and activation of the coagulation pathway. It results in end-organ micro thrombosis, and a progressive increase in capillary permeability, eventually resulting in loss of circulatory integrity.

[0222] Stage 4 is characterized by CARS taking over SIRS, resulting in a state of relative immunosuppression. The individual, therefore, becomes susceptible to secondary or nosocomial infections, thus perpetuating the sepsis cascade.

[0223] Stage 5 manifests in MODS with persistent dysregulation of both SIRS and CARS response.

[0224] In other embodiments, the acute inflammatory condition is associated with acute respiratory distress syndrome (ARDS). In exemplary embodiments, the subject may have one or more symptoms selected from mild, moderate or severe hypoxemia as determined by Partial Pressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end-expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness, rapid breathing, organ failure, chest pain, bluish coloring of nails or lips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation.

[0225] In some embodiments, the acute inflammatory condition is associated with severe acute respiratory syndrome (SARS) wherein, for example, the subject may have one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure.

[0226] The invention further provides a method of treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. Further provided is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection; a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection; and a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.

[0227] Suitable embodiments of the compounds of Formulae I, II, III, IV, V, VI or VII are as discussed supra.

[0228] In some embodiments, the compound is a compound of Formula I, II or III or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula I, II or III or apharmaceutically acceptable salt thereof; especially a compound of Formula III or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of Formula I, II or III; especially a compound of Formula III.

[0229] In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt thereof; especially a compound of Formula VI or a pharmaceutically acceptable salt thereof. In particular embodiments, the compound is a compound of Formula IV, V or VI; especially a compound of Formula VI.

[0230] In some embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such as MERS-CoV. In specific embodiments, the coronavirus is an ACE2-binding coronavirus, such as a lineage B betacoronavirus, including SARS-CoV or SARS-CoV-2.

[0231] In particular embodiments, the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0232] Symptoms associated with CRS include, but are not limited to, one or more selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination.

[0233] Non-limiting symptoms associated with a cytokine storm include one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof.

[0234] The CRS or cytokine storm may be associated with a MIS-C. In such embodiments, the subject may have one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0235] In some embodiments, the CRS or cytokine storm is associated with a SIRS, such as Stage 1 SIRS, Stage 2 SIRS, Stage 3 SIRS, Stage 4 SIRS or Stage 5 SIRS.

[0236] In some embodiments, the CRS or cytokine storm is associated with ARDS. For example, the subject may have one or more symptoms selected from mild, moderate or severe hypoxemia as determined by Partial Pressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end-expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness, rapid breathing, organ failure, chest pain, bluish coloring of nails or lips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation.

[0237] In particular embodiments, the CRS or cytokine storm is associated with SARS. For example, the subject may have one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro- inflammatory mediators, vascular leakage and organ failure.

[0238] The treatment of SARS is also contemplated. Accordingly, a further aspect of the invention provides a method of treating SARS in a subject, wherein the SARS is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. Also provided herein is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating SARS in a subject, wherein the SARS is associated with a coronavirus infection; a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating SARS in a subject, wherein the SARS is associated with a coronavirus infection; and a use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.

[0239] Suitable embodiments of the compounds of Formulae I, II, III, IV, V, VI and VII are as discussed supra.

[0240] In some embodiments, the coronavirus is a betacoronavirus, such as a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus or a lineage D betacoronavirus. In some embodiments, the betacoronavirus is a lineage B betacoronavirus, such as SARS-CoV or SARS-CoV-2; especially SARS-CoV-2. In alternative embodiments, the betacoronavirus is a lineage C betacoronavirus, such asMERS-CoV. In specific embodiments, the coronavirus is an ACE2-binding coronavirus, such as a lineage B betacoronavirus, including SARS-CoV or SARS-CoV-2.

[0241] The subject may have, for example, one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure, or any combination thereof.

[0242] In some embodiments, the SARS is associated with presence of CRS or a cytokine storm, for example, wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.

[0243] The SARS may also be associated with a MISC-C wherein, for example, the subject may have one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new.

[0244] The SARS may also be associated with a SIRS. For example, the subject may have Stage 1 SIRS, Stage 2 SIRS, Stage 3 SIRS, Stage 4 SIRS or Stage 5 SIRS.

[0245] In a further aspect, there is provided a method of antagonizing a viral fusion protein, comprising contacting a virus expressing a viral fusion protein with a compound of the invention. Further contemplated is a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in antagonizing a viral fusion protein, and use of a compound of Formula I, II, III or IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for antagonizing a viral fusion protein.

[0246] Preferably, the viral fusion protein is antagonized in a subject, thereby treating or inhibiting the development of a viral infection. Accordingly, also provided is a method of antagonizing a viral fusion protein in a subject, comprising administering to the subject compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein the compound contacts a virus expressing the fusion protein and antagonizes the fusion protein. In another aspect,there is provided a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in antagonizing a viral fusion protein in a subject, wherein the compound contacts a virus expressing the fusion protein and antagonizes the fusion protein; use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for antagonizing a viral fusion protein in a subject, wherein the compound contacts a virus expressing the fusion protein and antagonizes the fusion protein; and use of a compound of Formula I, II, III, IV, V, VI or VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for antagonizing a viral fusion protein in a subject, wherein the compound contacts a virus expressing the fusion protein and antagonizes the fusion protein.

[0247] Suitable embodiments of the virus and compounds are as discussed supra.

[0248] In some embodiments, the viral fusion protein is a spike protein.

[0249] As discussed herein, in particular embodiments, the virus is a coronavirus, such as SARS-CoV, SARS-CoV-2 or MERS; especially SARS-CoV-2. Accordingly, in particular embodiments, the viral fusion protein is a coronavirus spike protein, such as a SARS-CoV spike protein, SARS-CoV-2 spike protein or MERS spike protein; especially a SARS-CoV or SARS-CoV-2 spike protein; most especially a SARS- CoV-2 spike protein.

[0250] Antagonizing the viral fusion protein inhibits at least one activity of the fusion protein. In particular embodiments, the at least one activity of the viral fusion protein is one or both of binding of the virus to a host cell and entry of the virus into the cell; preferably both binding of the virus to a host cell and entry of the virus into the cell. Suitable host cells include a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell. In particular embodiments, the cell is a cell of the respiratory tract. In preferred embodiments, the cell is an ACE2 polypeptide-expressing cell.

[0251] While administration to any subject is contemplated, in any one of the above aspects, the subject has or is suspected of having a viral infection, or has been exposed to or is at risk of being exposed to a virus capable of causing a viral infection. In particular embodiments, the subject is a human.

[0252] Without wishing to be bound by theory, the compounds of the invention are proposed to bind to the fusion protein and directly inhibit interaction with the host cell, especially a surface protein on the host cell, for example, by binding to the fusionprotein at the surface protein binding site; or to bind to the fusion protein and cause a conformational change in the fusion protein, thereby inhibiting interaction with the host cell (e.g. the conformational change inhibits binding of the fusion protein to a surface protein on the host cell). Accordingly, while the compounds may bind to the fusion protein at the binding site of a host cell surface protein (either completely or partially), the compounds may alternatively bind to the fusion protein at a site which is distinct from the binding site of a host cell surface protein.

[0253] While administration of a single compound is contemplated, the invention further contemplates administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject in any one of the above aspects. The second compound may be administered concurrently with the first compound, for example, in a single composition. Without wishing to be bound by theory, it is thought that administration of two distinct compounds of the invention may result in an enhanced inhibition of the viral fusion protein. For example, it is proposed that concurrent administration of one compound that directly binds to the host cell surface protein binding site of the viral fusion protein and one compound that binds to a distinct site which causes a conformational change in the viral fusion protein. In some embodiments, the method comprises administering a compound of Formula II or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula III or a pharmaceutically acceptable salt, solvate or prodrug thereof. In particular embodiments, the method comprises administering a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0254] Any one of the aspects described above may involve administration of an effective amount of the compound of the invention as described in Section 3 supra. The compound may be administered in the form of, for example, a pharmaceutical composition as described herein. The compound of the invention may be administered to the subject by any route of administration suitable to effect treatment or inhibition of the development of the viral infection, treatment of the condition or antagonism of the fusion protein. A skilled person will be well aware of suitable routes of administration, such as one or more of the routes of administration discussed in Section 3 supra. For example, in some embodiments, the compound is administered by oral, inhalation, intranasal, topical or intravenous administration; especially inhalation or intranasal administration.

[0255] The dosage and frequency of administration will depend on the subject, the disorder to be treated and the route of administration. A skilled person will readily be able to determine suitable dosages and frequency of such dosages. For example, thecompound may be administered in an amount in the range of from about 0.25 μg to about 2000 mg, and may be administered at a frequency of, for example, once daily, or twice or three times daily. The treatment may be continued for multiple days, weeks, months or years. In embodiments where the pharmaceutical composition comprises one or more additional active agents, the dosages and frequency of administration are determined by reference to the usual dose and manner of administration of the said agents.

[0256] Any one of the methods described above may, in some embodiments, involve the administration of one or more further active agents as described in Section 3 supra, such as an antimicrobial agent (e.g. an antiviral).

[0257] A skilled person would be well aware of suitable assays used to evaluate the antagonism of a viral fusion protein. For example, the method may include contacting a virus or cell expressing a viral fusion protein (e.g. a spike protein) with a compound and screening for the inhibition of binding of a fusion protein binding partner, such as ACE2 (e.g. a ligand binding assay). Alternatively, the method may include screening for the inhibition of the activity, presence or expression of a downstream cellular target or product (e.g. viral entry into a host cell or the presence of a viral infection in a subject, such as an animal model). Detecting such binding, activity, presence or expression may be achieved utilizing techniques including, but not limited to, ELISA, a ligand binding assay (e.g. a radioligand binding assay or fluorescence binding assay), surface plasmon resonance, immunofluorescence, Western blots, immunoprecipitation, immunostaining, scintillation proximity assays or cell proliferation assays. Commercially available kits and / or products may also be used, such as SARS- CoV-2 Spike-ACE2 Interaction Inhibitor Screening Assay Kit (Catalogue No. 502050; Cayman Chemical, Ann Arbor, Michigan, USA); or a Spike S1 (SARS-CoV-2): ACE2 Inhibitor Screening Colorimetric Assay Kit (Catalogue No. 79954; BPS Bioscience, San Diego, California, USA).

[0258] The interaction of a virus with an ACE2-expressing cell may also be assessed using standard techniques, such as binding assays discussed above (including ligand binding assays, ELISA, surface plasmon resonance, and the like) which detect, for example, the interaction with a viral protein (e.g. a spike protein) with ACE2, or an assay which determines the viral infection of a host cell using, for example, immunostaining. Animal models may also be used to assess viral infection. EMBODIMENTS

[0259] Exemplary embodiments include, but are not limited to: 1. A compound of Formula I, II or III:o a p a aceu ca y accepa e sa , sovae o po ug eeo, wherein: L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene;L2, L5and L14are independently selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X1, X2, X3, X4, X5, X6, X7, X8, X9, X10and X11are independently selected from CH and N; and R1is selected from optionally substituted C2-C12 alkyl, optionally substituted C2-C12 alkenyl and optionally substituted C2-C12 alkynyl. 2. The compound according to embodiment 1, wherein X1-X11are CH. 3. The compound according to embodiment 1 or embodiment 2, wherein L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C3 alkylene, optionally substituted C2-C3 alkenylene and optionally substituted C2-C3 alkynylene. 4. The compound according to embodiment 3, wherein L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are optionally substituted C1-C3 alkylene. 5. The compound according to embodiment 4, wherein L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are methylene. 6. The compound according to any one of embodiments 1-5, wherein L2is selected from optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene. 7. The compound according to embodiment 6, wherein L2is optionally substituted C2-C5alkylene. 8. The compound according to embodiment 7, wherein L2is propylene. 9. The compound according to any one of embodiments 1-8, wherein L5is selected from optionally substituted C3-C6 alkylene, optionally substituted C3-C6 alkenylene and optionally substituted C6-C6 alkynylene. 10. The compound according to embodiment 9, wherein L5is optionally substituted C3-C6 alkylene. 11. The compound according to embodiment 10, wherein L5is butylene. 12. The compound according to any one of embodiments 1-11, wherein L14is selected from optionally substituted C2-C4 alkylene, optionally substituted C2-C4 alkenylene and optionally substituted C2-C4 alkynylene. 13. The compound according to embodiment 12, wherein L14is optionally substituted C2-C4 alkylene. 14. The compound according to embodiment 13, wherein L14is ethylene. 15. The compound according to any one of embodiments 1-14, wherein R1is selected from optionally substituted C6-C10alkyl, optionally substituted C6-C10alkenyl and optionally substituted C6-C10 alkynyl.16. The compound according to embodiment 15, wherein R1is optionally substituted C6-C10 alkyl. 17. The compound according to embodiment 16, wherein R1is octyl. 18. The compound according to any one of embodiments 1-17, wherein the compound is a compound of Formula IV: or19. The compound according to any one of embodiments 1-17, wherein the compound is a compound of Formula V:20. The compound according to any one of embodiments 1-17, wherein the compound is a compound of Formula VI:21. The compound according to any one of embodiments 1-20, wherein the compound is in the form of a salt and the salt is the sodium salt. 22. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 and a pharmaceutically acceptable carrier or diluent. 23. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 for use in therapy.24. A method of treating or inhibiting the development of a viral infection in a subject comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject:25. The method according to embodiment 24, wherein the infection is caused by a virus expressing a viral fusion protein. 26. The method according to embodiment 24 or embodiment 25, wherein the infection is caused by an enveloped virus. 27. The method according to any one of embodiments 24-26, wherein the infection is caused by a virus that interacts with an ACE2 polypeptide-expressing cell. 28. The method according to any one of embodiments 24-27, wherein the viral infection is a coronavirus infection. 29. The method according to embodiment 28, wherein the coronavirus is capable of causing severe acute respiratory syndrome (SARS). 30. The method according to embodiment 28 or embodiment 29, wherein the coronavirus is a betacoronavirus. 31. The method according to embodiment 30, wherein the betacoronavirus is selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. 32. The method according to embodiment 31, wherein the betacoronavirus is a lineage B betacoronavirus. 33. The method according to embodiment 32, wherein the lineage B betacoronavirus is selected from SARS-CoV and SARS-CoV-2. 34. The method according to embodiment 33, wherein the lineage B betacoronavirus is SARS-CoV-2. 35. The method according to embodiment 31, wherein the betacoronavirus is a lineage C betacoronavirus. 36. The method according to embodiment 35, wherein the lineage C betacoronavirus is MERS-CoV. 37. The method according to any one of embodiments 24-36, wherein the compound is administered by oral, inhalation, intranasal, topical or intravenous administration.38. The method according to any one of embodiments 24-37, further comprising administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof. 39. The method according to embodiment 38, wherein the method comprises administering a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. 40. A method of inhibiting the interaction of a virus with an ACE2 polypeptide- expressing cell, comprising, consisting or consisting essentially of contacting the virus with a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof. 41. The method according to embodiment 40, wherein the interaction is one or both of binding of the virus to the cell and entry of the virus into the cell. 42. The method according to embodiment 40 or embodiment 41, wherein the cell is a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell. 43. The method according to any one of embodiments 40-42, wherein the cell is a cell of the respiratory tract. 44. The method according to any one of embodiments 40-43, wherein the virus is a coronavirus. 45. The method according to embodiment 44, wherein the coronavirus is capable of causing SARS. 46. The method according to embodiment 44 or embodiment 45, wherein the coronavirus is a betacoronavirus. 47. The method according to embodiment 46, wherein the betacoronavirus is selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. 48. The method according to embodiment 47, wherein the betacoronavirus is a lineage B betacoronavirus. 49. The method according to embodiment 48, wherein the lineage B betacoronavirus is selected from SARS-CoV and SARS-CoV-2. 50. The method according to embodiment 49, wherein the lineage B betacoronavirus is SARS-CoV-2. 51. The method according to embodiment 47, wherein the betacoronavirus is a lineage C betacoronavirus.52. The method according to embodiment 51, wherein the lineage C betacoronavirus is MERS-CoV. 53. The method according to any one of embodiments 40-52, wherein the compound is administered by oral, inhalation, intranasal, topical or intravenous administration. 54. The method according to any one of embodiments 40-53, further comprising administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof. 55. The method according to embodiment 54, wherein the method comprises administering a compound of Formula V or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of Formula VI or a pharmaceutically acceptable salt, solvate or prodrug thereof. 56. A method of treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. 57. The method according to embodiment 56, wherein the coronavirus is a betacoronavirus. 58. The method according to embodiment 57, wherein the betacoronavirus is selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. 59. The method according to embodiment 58, wherein the betacoronavirus is a lineage B betacoronavirus. 60. The method according to embodiment 59, wherein the lineage B betacoronavirus is selected from SARS-CoV and SARS-CoV-2. 61. The method according to embodiment 60, wherein the lineage B betacoronavirus is SARS-CoV-2. 62. The method according to embodiment 58, wherein the betacoronavirus is a lineage C betacoronavirus. 63. The method according to embodiment 62, wherein the lineage C betacoronavirus is MERS-CoV. 64. The method according to any one of embodiments 56-63, wherein the acute inflammatory condition is associated with presence of cytokine release syndrome (CRS) or a cytokine storm. 65. The method according to embodiment 64, wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokinesor chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8. 66. The method according to embodiment 64 or embodiment 65, wherein the subject has CRS and has one or more symptoms selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. 67. The method according to embodiment 64 or embodiment 65, wherein the subject has a cytokine storm and has one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof. 68. The method according to any one of embodiments 56-67, wherein the acute inflammatory condition is associated with a multisystem inflammatory syndrome in children (MIS-C). 69. The method according to embodiment 68, wherein the subject has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new. 70. The method according to any one of embodiments 56-59, wherein the acute inflammatory condition is associated with a systemic inflammatory response syndrome (SIRS). 71. The method according to embodiment 70, wherein the subject has Stage 1 SIRS. 72. The method according to embodiment 70, wherein the subject has Stage 2 SIRS. 73. The method according to embodiment 70, wherein the subject has Stage 3 SIRS. 74. The method according to embodiment 70, wherein the subject has Stage 4 SIRS. 75. The method according to embodiment 70, wherein the subject has Stage 5 SIRS. 76. The method according to any one of embodiments 56-69, wherein the acute inflammatory condition is associated with acute respiratory distress syndrome (ARDS). 77. The method according to embodiment 76, wherein the subject has one or more symptoms selected from mild, moderate or severe hypoxemia as determined by PartialPressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end- expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness, rapid breathing, organ failure, chest pain, bluish coloring of nails or lips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation. 78. The method according to any one of embodiments 56-69, wherein the acute inflammatory condition is associated with SARS. 79. The method according to embodiment 78, wherein the subject has one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure. 80. A method of treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. 81. The method according to embodiment 80, wherein the coronavirus is a betacoronavirus. 82. The method according to embodiment 81, wherein the betacoronavirus is selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. 83. The method according to embodiment 82, wherein the betacoronavirus is a lineage B betacoronavirus. 84. The method according to embodiment 83, wherein the lineage B betacoronavirus is selected from SARS-CoV and SARS-CoV-2. 85. The method according to embodiment 84, wherein the lineage B betacoronavirus is SARS-CoV-2. 86. The method according to embodiment 82, wherein the betacoronavirus is a lineage C betacoronavirus. 87. The method according to embodiment 86, wherein the lineage C betacoronavirus is MERS-CoV. 88. The method according to any one of embodiments 80-87, wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokines or chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8.89. The method according to any one of embodiments 80-88, wherein the subject has CRS and has one or more symptoms selected from fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. 90. The method according to any one of embodiments 80-89, wherein the subject has a cytokine storm and has one or more symptoms selected from high fever, swelling and redness, extreme fatigue, nausea, bleeding, clotting, internal organ injury, and shock, or any combination thereof. 91. The method according to any one of embodiments 80-90, wherein the CRS or cytokine storm is associated with a MIS-C. 92. The method of embodiment 91, wherein the subject has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new. 93. The method according to any one of embodiments 80-90, wherein the CRS or cytokine storm is associated with a SIRS. 94. The method according to embodiment 93, wherein the subject has Stage 1 SIRS. 95. The method according to embodiment 93, wherein the subject has Stage 2 SIRS. 96. The method according to embodiment 93, wherein the subject has Stage 3 SIRS. 97. The method according to embodiment 93, wherein the subject has Stage 4 SIRS. 98. The method according to embodiment 93, wherein the subject has Stage 5 SIRS. 99. The method according to any one of embodiments 80-90, wherein the CRS or cytokine storm is associated with ARDS. 100. The method according to embodiment 99, wherein the subject has one or more symptoms selected from mild, moderate or severe hypoxemia as determined by Partial Pressure of arterial oxygen / Fraction of inspired oxygen (PaO2 / FiO2) or positive end- expiratory pressure (PEEP), bilateral opacities, respiratory failure, shortness of breath, labored breathing, cough, fever, increased heart rate, low blood pressure, confusion, extreme tiredness, rapid breathing, organ failure, chest pain, bluish coloring of nails orlips, an change in the level of one or more inflammatory markers, or need for mechanical ventilation. 101. The method according to any one of embodiments 80-90, wherein the CRS or cytokine storm is associated with SARS. 102. The method according to embodiment 101, wherein the subject has one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure. 103. A method of treating SARS in a subject, wherein the SARS is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject. 104. The method according to embodiment 103, wherein the coronavirus is a betacoronavirus. 105. The method according to embodiment 104, wherein the betacoronavirus is selected from a lineage A betacoronavirus, a lineage B betacoronavirus, a lineage C betacoronavirus and a lineage D betacoronavirus. 106. The method according to embodiment 105, wherein the betacoronavirus is a lineage B betacoronavirus. 107. The method according to embodiment 106, wherein the lineage B betacoronavirus is selected from SARS-CoV and SARS-CoV-2. 108. The method according to embodiment 107, wherein the lineage B betacoronavirus is SARS-CoV-2. 109. The method according to embodiment 105, wherein the betacoronavirus is a lineage C betacoronavirus. 110. The method according to embodiment 109, wherein the lineage C betacoronavirus is MERS-CoV. 111. The method according to any one of embodiments 103-110, wherein the subject has one or more symptoms selected from acute febrile illness, malaise, fatigue, headache, flushing, diarrhea, nausea, vomiting, coughing including dry coughing, sore throat, runny nose, nasal congestion, production of pro-inflammatory mediators, vascular leakage and organ failure, or any combination thereof. 112. The method according to any one of embodiments 103-111, wherein the SARS is associated with presence of CRS or a cytokine storm. 113. The method according to embodiment 112, wherein the CRS or cytokine storm comprises an elevation of at least 50% compared to basal state of one or more cytokinesor chemokines selected from IFN-γ, IFN-β, TNF-α, IL-1β, IL-6, IL-17A, CCL3, CXCL2 and CXCL8. 114. The method according to any one of embodiments 103-113, wherein the SARS is associated with a MISC-C. 115. The method according to embodiment 114, wherein the subject has one or more symptoms selected from fever, vomiting, diarrhea, stomach pain, skin rash, red eyes, redness or swelling of the lips and tongue, feeling unusually tired, redness or swelling of the hands or feet, severe stomach pain, cardiac symptoms, including chest pain, palpitations and shortness of breath, bluish lips or face, mental confusion, inability to wake up or stay awake, abdominal pain with vomiting and diarrhea, skin rash and swelling of extremities, faintness and low blood pressure that is new. 116. The method according to any one of embodiments 103-115, wherein the SARS is associated with a SIRS. 117. The method according to embodiment 116, wherein the subject has Stage 1 SIRS. 118. The method according to embodiment 116, wherein the subject has Stage 2 SIRS. 119. The method according to embodiment 104, wherein the subject has Stage 3 SIRS. 120. The method according to embodiment 116, wherein the subject has Stage 4 SIRS. 121. The method according to embodiment 116, wherein the subject has Stage 5 SIRS. 122. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating or inhibiting the development of a viral infection in a subject. 123. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection. 124. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.125. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating SARS in a subject, wherein the SARS is associated with a coronavirus infection. 126. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating or inhibiting the development of a viral infection in a subject. 127. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection. 128. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection. 129. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of embodiments 1-21 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.

[0260] In order that the invention may be readily understood and put into practical effect, particular preferred embodiments will now be described by way of the following non-limiting examples. EXAMPLES

[0261] All starting materials, reagents and equipment used are commercially available (e.g. from Sigma-Aldrich (Burlington, MA, USA) and the like) and were obtained from commercial sources unless otherwise indicated.

[0262] Unless stated otherwise, all reactions were conducted in an atmosphere of nitrogen. NMR spectra were collected using a Bruker Ultraspin 400 MHz spectrometer (1H 400 MHz;13C 100 MHz). Flash chromatography was conducted using Merck silica gel 60 μm. Reactions were monitored by thin layer chromatography (TLC) using Merck silica gel 60 μm TLC plates with aluminium backing and containing F254 fluorescent indicator. Compounds were visualized on the TLC plates using ultraviolet light followed by staining with potassium permanganate solution containing KMnO4 (1.5 g), K2CO3 (10 g), 10% NaOH solution (1.25 mL) diluted to 200 mL with deionized water or by staining with asolution containing 10% H2SO4 in ethanol. All organic extracts were dried with anhydrous magnesium sulphate unless otherwise stated and filtered prior to removal of the solvent under reduced pressure. EXAMPLE 1 – Synthesis of 2,3,3’,4’,6-penta-O-acetyl sucralose (compound 1)

[0263] To a stirred solution of sucralose (6.1 g, 15 mmol) in pyridine (80 mL) was added acetic anhydride (15 mL, 100 mmol). The mixture was then stirred at room temperature (r.t.) for 24 hours (h.) and concentrated by co-evaporating pyridine with toluene. The crude material was dissolved in ethyl acetate (EtOAc) (100 mL) and washed with 1M HCl (2 × 100 mL), 5% aq. NaHCO3 (100 mL), brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to obtain a glassy solid. The crude material was recrystallized from toluene to obtain 2,3,3’,4’,6-penta-o-acetyl sucralose 1 (8.5 g, 97%) as needle like crystals.1H NMR (CDCl3, 400 MHz): 5.67 (d, 1H, J3’,4’ = 6.4 Hz, H-3’), 5.65 (d, J1,2 = 2.0 Hz, H-1), 5.29-5.27 (m, 2H, H-2, H-3), 4.58-4.52 (m, 2H, H-4, H-5), 4.27- 4.19 (m, 3H, H-5’, H-6a, H-6b), 3.75 (dd, 2H, J5’,6’ = 6.2 Hz, J6’a,6’b = 0.7 Hz, H-6’a, H- 6’b), 3.69, 3.57 (ABq, 2H, J = 12. 1 Hz, H-1’), 2.12 (s, 3H, CH3), 2.11 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.07 (s, 3H, CH3);13C NMR (CDCl3, 100 MHz): 170.4, 170.2, 170.0, 169.8, 169.6 (5 × COCH3), 104.4 (C-2’), 90.7 (C-1), 80.8 (C-5’), 77.2, 76.1 (C-4’), 75.9 (C-3’), 68.0 (C-2), 67.8 (C-4), 66.9 (C-3), 63.6 (C-6), 59.0 (C-5), 44.5 (C-1’), 43.9 (C-6’), 20.8, 20.7 (×2), 20.5 (5 × COCH3). EXAMPLE 2 – Synthesis of 2,3,3’,4’,6-penta-O-acetyl-6’-azido sucralose (compound 2)

[0264] 2,3,3’,4’,6-penta-O-acetyl sucralose 1 (prepared according to Example 1) (35 g, 57 mmol) was dissolved in dimethylsulfoxide (DMSO) (100 mL) followed by the addition of sodium azide (10 g, 154 mmol) and the resulting solution heated at 80°C for 48 h. The reaction was cooled to room temperature and partitioned between diethyl ether (Et2O) (300 mL) and water (300 mL). The organic layer was washed twice withwater (2 x 400 mL) and all three water layers were re-extracted with Et2O (200 mL). The combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The resulting yellow gum was dissolved in a minimal amount of EtOAc (~50 mL) followed by a small amount of petrol until cloudy. The addition of a seed crystal and scratching yielded a precipitate that continued to form as more petrol was slowly added with scratching. The resulting precipitate was filtered and washed with 1:4 EtOAc / petrol to give 2,3,3’,4’,6-penta-O-acetyl-6’-azido sucralose 2 as a white powder (20 g, 56%).1H NMR (CDCl3, 400 MHz): 5.68 (d, 1H, J3’-4’ = 6.9 Hz, H-3’), 5.64 (d, 1H, J1,2 = 3.6 Hz, H-1), 5.32 (dd, 1H, J2,3 = 10.7 Hz, H-3), 5.32-5.29 (m, 1H, H-4’), 5.25 (dd, 1H, H-2), 4.58-4.49 (m, 2H, H-4, H-5), 4.24-4.20 (m, 2H, H-6a, H-6b), 4.15-4.08 (m, 1H, H-5’), 3.69, 3.58 (ABq, 2H, J = 12.1 Hz, H-1’), 3.64-3.56 (m, 1H, H-6’a), 3.50 (dd, 1H, J6a’,6b’ = 4.1 Hz, J5,6b’= 13.3 Hz, H-6b’), 2.10 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.06 (s, 3H, CH3), 2.05 (s, 3H, CH3);13C NMR (CDCl3, 100 MHz): 170.3, 170.1, 170.0, 169.9, 169.7 (5 × COCH3), 104.1 (C-2’), 90.8 (C-1), 80.0 (C-5’), 75.6 (C-3’), 75.1 (C- 4’), 67.9 (C-3), 67.7 (C-5), 67.0 (C-2), 63.4 (C-6), 58.9 (C-4), 52.5 (C-6’), 44.5 (C-1’), 20.7, 20.6, 20.6, 20.6, 20.4 (5 × COCH3); HRMS (ESI); m / z [M + Na]+calculated for C22H29Cl2N3O13Na; found 636.0994. EXAMPLE 3 – Synthesis of 1,2,3,4,6-penta-O-acetyl-D-mannopyranose (compound 3)

[0265] Acetic anhydride (20.7 mL, 160 mmol) was added to a mixture of D- mannose (3.0 g, 10.6 mmol) and sodium acetate (1.6 g, 20 mmol). The reaction mixture was then stirred at 80°C for 4 h. and poured into cold saturated (sat.) NaHCO3 solution (100 mL). The mixture was then stirred for 1 h., extracted with dichloromethane (DCM) (2 × 100 mL), dried (MgSO4) and concentrated under reduced pressure. 1,2,3,4,6-penta- O-acetyl-D-mannopyranose 3 (3.5 g, 85%, α / β 1:0.4) was obtained as a colorless oil. The crude material was used in the subsequent step without further purification.1H NMR (CDCl3, 400 MHz): 6.06 (d, 1H, J = 1.1 Hz), 5.84 (d, 0.4 H, J = 1.3 Hz), 5.46 (dd, 0.4H, J = 1.1 Hz, J = 3.3 Hz), 5.34-5.32 (m, 2H), 5.28 (d, 0.4H, J = 9.9 Hz), 5.25-5.22 (m, 1H), 5.11 (dd, 0.4H, J = 3.3 Hz, J = 10.0 Hz), 4.28 (dd, 0.4H, J = 5.4 Hz, J = 12.5 Hz), 4.26 (dd, 1H, J = 4.9 Hz, J = 12.3 Hz), 4.15-3.98 (m, 2.4H), 3.78 (ddd, 0.4H, J = 2.4 Hz, J = 5.3 Hz, J = 7.8 Hz), 2.19 (s, 1.2H, OCH3), 2.16 (s, 3H, OCH3), 2.15 (s, 3H, OCH3), 2.08 (s, 1.3H, OCH3), 2.07 (s, 4H, OCH3), 2.03 (s, 4H, OCH3), 1.99 (s, 4H, OCH3).EXAMPLE 4 – Synthesis of propynyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside (compound 4)

[0266] Propargyl was added to a stirred solution of1,2,3,4,6-penta-O-acetyl-D-mannopyranose 3 (prepared according to Example 3) (1.5 g, 3.8 mmol) in dry DCM (20 mL). The mixture was cooled to 0°C and BF3.OEt2 (4.9 mL, 38.4 mmol) was added dropwise. The resulting mixture was stirred for 15 min, brought to r.t., and the stirring was continued for 24 h. The reaction mixture was diluted with DCM (100 mL) and poured into ice-cold sat. NaHCO3 (100 mL) solution. The resulting mixture was stirred until bubbling seized. The organic phase was then separated and washed with (3 × 50 mL) sat. NaHCO3, water (100 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was then purified by recrystallizing with petroleum spirit (Pet. Sp.) / EtOAc (8:1) to obtain propynyl 2,3,4,6-tetra-O-acetyl-α-D- mannopyranoside 4 (1.2 g, 85%) as colorless needle like crystals.1H NMR (CDCl3, 400 MHz): 5.33 (dd, 1H, J2,3 = 3.2 Hz, J3,4 = 9.8 Hz, H-3), 5.29 (d, 1H, J3,4 = J4,5 = 9.3 Hz, H-4), 5.26 (dd, 1H, J1,2 = 1.8 Hz, J2,3 = 3.2 Hz, H-2), 5.01 (d, 1H, J1,2 = 1.8 Hz, H-1), 4.30-4.24 (m, 3H, H-6a, CH2C≡CH), 4.09 (dd, J5,6b = 2.5 Hz, J6a,6b = 12.3 Hz, H-6b), 4.00 (ddd, 1H, J4,5 = 9.2 Hz, J5,6b = 2.5 Hz, J5,6a = 5.3 Hz, H-5), 2.45 (t, 1H, J = 2.4 Hz, CH2C≡CH), 2.14 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.97(s, 3H, CH3);13C NMR (CDCl3, 100 MHz): 170.6, 169.9, 169.8, 169.7 (4 × CH3CO), 96.3 (C-1), 77.9 (OCH2C≡CH), 75.6 (OCH2C≡CH), 69.3 (C-2), 69.0 (C-3), 68.8 (C-5), 66.1 (C-4), 62.3 (C-6), 55.0 (OCH2C≡CH), 20.9, 20.7 (2 ×), 20.6 (4 × CH3CO); HRMS (ESI); m / z [M + Na]+calculated for C17H22O10Na; found 409.1121. EXAMPLE 5 – Synthesis of propynyl 2,3,4-tri-O-benzoyl-6-toluenesulfonyl-α-D- mannopyranoside (compound 5)

[0267] A catalytic amount of sodium metal (~ 4 mg) was dissolved in methanol (MeOH) (50 mL). The resulting solution was added to a solution of propynyl 2,3,4,6- tetra-O-acetyl-α-D-mannopyranoside 4 (prepared according to Example 4) (50.0 g, 130 mmol) in MeOH (500 mL), and the mixture was stirred at 45°C for 1 h. The reaction mixture was then neutralized with pre-washed acidic ion exchange resin (IR-120 H+), filtered and concentrated under reduced pressure. The residue was dissolved in a minimal amount of methanol. The product was precipitated by a portionwise addition of ethyl acetate. The mixture was filtered to give a light yellow / brown solid (25.5 g, 90%). The crude material was dissolved in anhydrous pyridine (200 mL) and toluenesulfonyl chloride (30 g, 157 mmol) was added to the reaction mixture and allowed to stand at room temperature for 18 h. Benzoyl chloride (50 mL, 60 g, 426 mmol) was added and allowed to stand at room temperature for 4 h. Water (50mL) was added to the reaction mixture and it evaporated to dryness. The crude residue obtained was dissolved in EtOAc (1000 mL) and washed with 1 M HCl (2 × 500 mL), sat. NaHCO3 (500 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (15-35% EtOAc / Pet. Sp.) on silica gel to afford propynyl 2,3,4-tri-O-benzoyl-6-toluenesulfonyl-α-D-mannopyranoside 5 (7.3 g, 70%) as a colorless oil.1H NMR (CDCl3, 400 MHz): 8.06 (dd, 2H, J = 1.1 Hz, J = 8.1 Hz, H-OBz), 7.90 (dd, 2H, J = 0.9 Hz, J = 8.1 Hz, H-OBz), 7.78 (dd, 2H, J = 1.2 Hz, J = 8.3 Hz, H- OBz), 7.62-7.18 (m, 8H, H-OBz), 7.13 (s, 2H, H-OTPS), 5.87 (dd, 1H, J2,3 = 3.3 Hz, J3,4 = 10.0 Hz, H-3), 5.75 (dd, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.67 (dd, 1H, J1,2 = 1.8 Hz, J2,3 = 3.3 Hz, H-2), 5.26 (d, 1H, J1,2 = 1.8 Hz, H-1), 4.47-4.40 (m, 1H, H-5), 4.32 (t, 2H, J = 2.9 Hz, CH2C≡CH), 4.29-4.25 (m, 2H, H-6), 4.08 (h, 2H, J = 6.9 Hz, J = 13.3 Hz, J = 20.1 Hz, CH-i-pr), 2.86 (h, 1H, J = 6.9 Hz, J = 13.3 Hz, J = 20.1 Hz, CH-i-pr), 2.48 (t, 1H, J = 2.4 Hz, CH2C≡CH), 1.22 (s, 3H, CH3), 1.19 (s, 3H, CH3), 1.18 (s, 3H, CH3), 1.17 (s, 3H, CH3), 1.15 (s, 3H, CH3);13C NMR (CDCl3, 100 MHz): 165.5, 165.3, 165.2 (3 × C=O), 153. 8, 150.9, 133.5, 129.9, 129.8, 129.7, 128.6, 128.4, 128.2, 123.7 (Ar-OTPS), 95.9 (C-1), 77.9, 77.2 (OCH2C≡CH), 75.8 (OCH2C≡CH), 70.2 (C-2), 69.7 (C-3), 69.6 (C- 5), 67.8 (C-6), 67.0 (C-4), 55.1 (OCH2C≡CH), 34.1 (CH-i-pr), 29.6 (CH-i-pr), 24.6, 24.5, 23.4 (6 × CH3); HRMS (ESI); m / z [M + Na]+calculated for C44H48O11NaS; found 819.2844. EXAMPLE 6 – Synthesis of compound 10 (G24)

[0268] The general synthetic scheme for compound 10 is shown below:PROCEDURE1FOR SYNTHESIS OFSO3.PY

[0269] To a solution of pyridine (4 mL) in DCM (20 mL) at 0°C, chlorosulfonic acid (1.6 mL) was added dropwise and the mixture stirred for 30 min. The reaction mixture was then filtered and the precipitate was washed with ice cold water (3 × 20 mL), ice cold sat. NaHCO3 (2 × 10 mL), ice cold water (2 × 10 mL) (until the pH of the filtrate was 7), cold ethanol (EtOH) (2 × 20 mL), cold toluene (10 mL) and cold DCM (10 mL). The precipitated SO3.Py was then thoroughly dried under high vacuum and used within 24 h.GENERAL PROCEDURE 1 FOR CLICK REACTION

[0270] Sodium ascorbate [2 equivalents (equiv.)] and copper sulfate pentahydrate (1 equiv.) were added to a mixture of azide analogue (1 equiv.) and alkyne analogue in 1,4-dioxane / H2O (3:1). The reaction mixture was then stirred at room temperature for 18 h. and filtered over a pad of celite. The filtrate was concentrated under reduced pressure and the crude material was dissolved in EtOAc. The organic layer was washed with 1M HCl, sat. NaHCO3, dried (MgSO4) and concentrated under reduced pressure. The crude material obtained was purified by flash column chromatography on silica gel to obtain the desired compound. GENERAL PROCEDURE1FOR ACETATE AND BENZOATE HYDROLYSIS

[0271] The oligosaccharide was dissolved in methanol followed by the portion wise addition of 30% aqueous (aq.) NH3 over 10 minutes to ensure the starting material did not oil out of solution. The resulting solution was left to stand at room temperature (24-48 h) before being concentrated and pre-adsorbed onto silica. Flash chromatography to remove both acetamide and benzamide returned the polyols as foams. GENERAL PROCEDURE 1 FOR SULFATION AND DIALYSIS

[0272] The polyol (100 mg) was dissolved in dimethylformamide (DMF) (10 mL) followed by the addition of freshly prepared SO3.Py (10 equiv. per hydroxyl group). The reaction was allowed to stand at room temperature (5 days) before being quenched with 5M NaOH solution (2 equiv. per SO3.Py). The resulting yellow-brown mixture was partitioned between water (20 mL) and CH2Cl2 (50 mL). The aqueous layer was washed again with CH2Cl2 before being concentrated. The resulting residue was dissolved in Milli- Q water (5-10 mL) and dialysed using approximately 30 cm of Cellulose membrane tubing with a molecular weight cut-off (MWCO) of 0.5 kD. The dialysis tube was washed with Milli-Q water prior to use, and the ends secured with clips. The tubes were placed in 4 litres of 0.1 M NaCl solution for 2 h and then 4 litres of Milli-Q water overnight. The dialysis tube expanded significantly to hold approximately 150 mL from the overnight dialysis. The contents of the dialysis tube was removed, concentrated to ~5 mL and transferred to a Microsep Advanced tube with a 1 kD MWCO Omega membrane (Pall Corporation, New York, USA). The tube was spun at 5000-7000 g to concentrate to ~200 μL before washing twice with 3 mL of Milli-Q water. The retained material was then passed through a C18 Sep-Pak by eluting with water (3 mL) followed by methanol (3 mL) to remove the majority of color remaining. The desired product was present in the water fraction as determined by thin layer chromatography (t.l.c.) (see below) and was freeze dried to return the sulfated glycanic as a powder.SYNTHESIS OF COMPOUND 6

[0273] Click reaction of 2,3,3’,4’,6-penta-O-acetyl-6’-azido sucralose 2 (prepared according to Example 2) (8.0 g, 13.0 mmol) and propynyl 2,3,4-tri-O-benzoyl- 6-toluene sulfonyl-α-D-mannopyranoside 5 (prepared according to Example 5) (8.0 g, 11.7 mmol) via general procedure 1 (72 h.) led to a yellow foam that was dissolved in DMF (100 mL) followed by the addition of sodium azide (1.5 g, 23.0 mmol). The resulting mixture was heated at 60°C for 48 h. before being partitioned between EtOAc (300 mL) and water (300 mL). The aqueous was re-extracted with EtOAc (200 mL) and the combined organics washed with water (2 x 300 mL), dried (MgSO4), concentrated and subjected to flash chromatography (40% – 60% EtOAc / Pet. Sp.) to return the azide 6 as a colorless foam (12.0 g, 88 %).1H NMR (CDCl3, 400 MHz): δ = 8.11-8.07 (m, 2H), 7.97-7.93 (m, 2H), 7.85 (s, 1H), 7.82-7.78 (m, 2H), 7.64-7.57 (m, 1H), 7.55-7.46 (m, 3H), 7.44-7.34 (m, 3H), 7.28-7.21 (m, 2H), 5.93-5.84 (m, 2H), 5.75 (d, 1H, J = 7.4 Hz), 5.74-5.72 (m, 1H), 5.69-5.67 (m, 1H), 4.43 (t, 1H, J = 7.3 Hz), 5.37-5.32 (m, 2H), 5.25 (d, 1H, J = 1.7 Hz), 5.02 (d, 1H, J = 12.5 Hz), 4.89 (dd, 1H, J = 3.7 and 14.4 Hz), 4.87 (d, 1H, J = 12.5 Hz), 4.76 (dd, 1H, J = 9.1 and 14.4 Hz), 4.64-4.58 (m, 2H), 4.49 (ddd, 1H, J = 3.6, 7.2 and 8.9 Hz), 4.41-4.32 (m, 1H), 4.36 (dd, 1H, J = 4.3 and 11.8 Hz), 4.27 (dd, 1H, J = 6.9 and 11.8 Hz), 3.64 (d, 1H, 11.9 Hz), 3.55 (d, 1H, 11.9 Hz), 3.53 (m, 2H), 2.16 (s, 3H), 2.12 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H), 2.01 (s, 3H). SYNTHESIS OF COMPOUND 7

[0274] Click reaction of azide 6 (12.0 g, 10.3 mmol) and propynyl 2,3,4-tri-O- benzoyl-6-toluene sulfonyl-α-D-mannopyranoside 5 (prepared according to Example 5) (7.0 g, 10.2 mmol) via general procedure 1 (24 h.) led to a foam that was dissolved inDMF (100 mL) followed by the addition of sodium azide (1.5 g, 23.0 mmol). The resulting mixture was heated at 60°C for 24 h. before being partitioned between EtOAc (300 mL) and water (300 mL). The aqueous was re-extracted with EtOAc (200 mL) and the combined organics washed with water (2 x 300 mL), dried (MgSO4), concentrated and subjected to flash chromatography (50% – 80% EtOAc / Pet. Sp.) to return the azide 7 as a light yellow foam (13.5 g, 77 %).1H NMR (CDCl3, 400 MHz): δ = 8.09-7.98 (m, 7H), 7.95-7.89 (m, 2H), 7.82-7.74 (m, 5H), 7.67-7.57 (m, 2H), 7.56-7.45 (m, 6H), 7.44-7.32 (m, 6H), 7.26-7.20 (m, 2H),(m, 6H), 5.66 (dd, 1H, J = 1.6 and 3.3 Hz), 5.61 (dd, 1H, J = 1.8 and 3.1 Hz), 5.42 (t, 1H, J = 7.3 Hz), 5.39 (dd, 1H, J = 3.5 and 10.7 Hz), 5.33 (dd, 1H, J = 3.3 and 10.8 Hz), 5.24-5.19 (m, 1H), 4.97 (d, 1H, J = 12.4 Hz), 4.88-4.56 (m, 10H), 4.47 (ddd, 1H, J = 3.6, 7.2 and 8.9 Hz), 4.37-4.30 (m, 1H), 4.33 (dd, 1H, J = 4.5 and 11.6 Hz), 4.26 (dd, 1H, J = 7.3 and 11.8 Hz), 3.65, 3.61 (ABq, 2H, J = 12.2 Hz), 3.65-3.44 (m, 2H), 2.16 (s, 3H), 2.09 (s, 3H), 2.09 (s, 3H), 2.07 (s, 3H), 1.96 (s, 3H). SYNTHESIS OF COMPOUND8

[0275] Click reaction of the azide 7 (5.0 g, 2.9 mmol) and 1,5-hexadiyne (50 % in pentane, 280 μL, 1.4 mmol) via general procedure 1 (48 h.) gave an incomplete reaction via t.l.c. A second portion of copper sulfate pentahydrate and sodium ascorbate was added and the reaction heated at 50°C for 4 h. t.l.c. indicated the reaction to be complete. A usual workup as per general procedure 1 followed by flash chromatography (80% – 100% EtOAc / Pet. Sp.) returned the dimer 8 as a light brown foam (3.0 g, 59%).1H NMR (CDCl3, 400 MHz): δ = 8.05-7.95 (m, 5H), 7.95-7.85 (m, 4H), 7.82-7.76 (m, 2H), 7.75-7.70 (m, 3H), 7.67-7.30 (m, 15H), 7.25-7.18 (m, 4H), 5.93-5.82 (m, 2H), 5.81-5.68 (m, 3H), 5.67-5.58 (m, 2H), 5.54 (dd, 1H, J = 1.6 and 3.1 Hz), 4.45-4.36 (m, 2H), 5.32 (dd, 1H, J = 3.3 and 10.9 Hz), 5.21 (d, J = 1.3 Hz), 5.15 (d, J = 1.3 Hz), 4.88- 4.51 (m, 13H), 4.50-4.42 (m, 1H), 4.33 (dd, 1H, J = 4.6 and 11.9 Hz), 4.24 (dd, 1H, J = 7.0 and 11.9 Hz), 3.68 (d, 1H, J = 12.0 Hz), 3.61 (d, 1H, J = 12.0 Hz), 3.09-3.01 (m, 2H), 2.15 (s, 3H), 2.07 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 1.95 (s, 3H).SYNTHESIS OF COMPOUND 9(200 mL) and 30% aq. NH3 (30 mL) according to general procedure 1 (24 h) gave, after flash chromatography (50% - 100% MeOH / EtOAc), the oligosaccharide 9 as a light brown foam (1.2 g, 81%);1H NMR (D2O, 400 MHz): δ = 7.89 (bs, 2H), 7.79 (s, 1H), 5.46 (d, 1H, J = 4.1 Hz), 4.94-4.85 (m, 2H), 4.62-4.51 (m, 2H), 4.48-4.32 (m, 4H), 4.31-4.13 (m, 6H), 3.95 (dd, 1H, J = 10.3 and 4.0 Hz), 3.92 (dd, 1H, J = 3.4 and 1.6 Hz), 3.90-3.74 (m, 6H), 3.70 (s, 2H), 3.65 (dd, 1H, J = 9.5 and 3.4 Hz), 3.61-3.53 (m, 2H), 2.97 (s, 2H). SYNTHESIS OF COMPOUND 10

[0277] Sulfation of the deprotected octomer 9 (100 mg, 0.05 mmol) according to general procedure 1 followed by dialysis gave the octomer 10 as a colorless powder (20 mg, 9%);1H NMR (D2O, 400 MHz): δ = 8.15 (s, 1H), 8.07 (s, 1H), 7.93 (bs, 1H), 5.88 (d, J = 3.6 Hz, 1H), 5.39 (d, J = 7.9 Hz, 1H), 5.30 (d, 1H, J = 1.9 Hz), 5.24 (d, 1H, J = 1.8 Hz), 5.17-5.05 (m, 2H), 5.05-4.85 (m, 8H), 4.78-4.61 (m, 4H), 4.59-4.21 (m, 11H), 4.00, 3.93 (ABq, 2H, J = 12.5 Hz). EXAMPLE 7 – Synthesis of propargyl maltotriose (compound 11)11

[0278] The general synthetic scheme is shown below:

[0279] Boron trifluoride diethyl etherate (46 mL) was added dropwise to a mixture of peracetate maltotriose (prepared according to the procedure of Su et al. (2019) Eur J Med Chem, 182: 111622) (13.3 g, 13.8 mmol) and propargyl alcohol (8.5 mL, 137 mmol) in dry DCM (500 mL) at 0°C. The mixture was then stirred at r.t. for 48 h. Sat. NaHCO3 (10 mL) was then added to the reaction mixture and stirred for a further 10 min. The organic layer was extracted, dried (MgSO4) and concentrated under reduced pressure. The crude material obtained was purified by flash column chromatography (3:1 EtOAc: Pet. Sp.) to obtain propargyl maltotriose 11 (6.0 g, 45%) as a glassy solid.1H NMR (CDCl3, 400 MHz): 5.43-5.22 (m, 6H), 5.04 (t, 1H, J = 10.0 Hz), 4.86-4.76 (m, 3H), 4.71 (dd, 1H, J = 4.1 Hz, J = 10. 4 Hz), 4.51-4.39 (m, 2H), 4.33 (d, 2H, J = 2.3 Hz), 4.32-4.13 (m, 4H), 4.06-3.87 (m, 6H), 3.77-3.69 (m, 1H), 2.44 (t, 1H, J = 2.4 Hz), 2.15, 2.13, 2.07, 2.02, 2.02, 2.00, 1.98, 1.97 (×2) (s, 3H, 9 × CH3);13C NMR (CDCl3, 100 MHz): 170.6 (×2), 170.5 (×2), 170.3, 170.1, 169.8, 169.7 (×2), 169.4, 97.5, 95.7 (×2), 77.2, 75.5, 75.2, 73.7, 72.5, 72.2, 71.8, 71.7, 70.4, 70.1, 69.4, 68.9, 68.5, 67.9, 62.8, 62.3, 61.4, 60.4, 55.8, 20.9, 20.8, 20.6, 20.5, 14.2; HRMS (ESI); m / z [M + Na]+calculated for C41H54O26Na; found 385.2792. EXAMPLE 8 – Synthesis of propynyl 2,3,4-tri-O-benzoyl-6-2,4,6-triisopropylbenzene sulfonyl-α-D-mannopyranoside (compound 12)

[0280] To a solution of propynyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside 4 (prepared according to Example 4) (5.0 g, 13 mmol) in MeOH (50 mL), a catalytic amount of sodium metal (~ 4 mg) was added and the mixture was stirred at r.t. for 2 h.The reaction mixture was then neutralized with pre-washed acidic ion exchange resin (IR-120 H+), filtered and concentrated under reduced pressure. The crude material was dissolved in anhydrous pyridine (50 mL) and cooled to 0°C. 2,4,6-triisopropylbenzene sulfonyl chloride (4.7 g, 16 mmol) was added to the reaction mixture and allowed to warm up to r.t., and stirred for 18 h. The reaction mixture was then cooled to 0°C and benzoyl chloride (5.0 mL, 47 mmol) was added and stirred at r.t. for 24 h. The reaction mixture was concentrated under reduced pressure by co-evaporating the pyridine with toluene. The crude residue obtained was dissolved in EtOAc (100 mL) and washed with 1 M HCl (2 × 50 mL), sat. NaHCO3 (50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (Pet. Sp. / EtOAc 3:1) on silica gel to afford propynyl 2,3,4-tri-O-benzoyl-6-2,4,6- triisopropylbenzene sulfonyl-α-D-mannopyranoside 12 (7.3 g, 70%) as a colorless oil.1H NMR (CDCl3, 400 MHz): 8.06 (dd, 2H, J = 1.1 Hz, J = 8.1 Hz, H-OBz), 7.90 (dd, 2H, J = 0.9 Hz, J = 8.1 Hz, H-OBz), 7.78 (dd, 2H, J = 1.2 Hz, J = 8.3 Hz, H-OBz), 7.62-7.18 (m, 8H, H-OBz), 7.13 (s, 2H, H-OTPS), 5.87 (dd, 1H, J2,3 = 3.3 Hz, J3,4 = 10.0 Hz, H-3), 5.75 (dd, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.67 (dd, 1H, J1,2 = 1.8 Hz, J2,3 = 3.3 Hz, H-2), 5.26 (d, 1H, J1,2 = 1.8 Hz, H-1), 4.47-4.40 (m, 1H, H-5), 4.32 (t, 2H, J = 2.9 Hz, CH2C≡CH), 4.29-4.25 (m, 2H, H-6), 4.08 (h, 2H, J = 6.9 Hz, J = 13.3 Hz, J = 20.1 Hz, CH-i-pr), 2.86 (h, 1H, J = 6.9 Hz, J = 13.3 Hz, J = 20.1 Hz, CH-i-pr), 2.48 (t, 1H, J = 2.4 Hz, CH2C≡CH), 1.22 (s, 3H, CH3), 1.19 (s, 3H, CH3), 1.18 (s, 3H, CH3), 1.17 (s, 3H, CH3), 1.15 (s, 3H, CH3);13C NMR (CDCl3, 100 MHz): 165.5, 165.3, 165.2 (3 × C=O), 153. 8, 150.9, 133.5, 129.9, 129.8, 129.7, 128.6, 128.4, 128.2, 123.7 (Ar-OTPS), 95.9 (C-1), 77.9, 77.2 (OCH2C≡CH), 75.8 (OCH2C≡CH), 70.2 (C-2), 69.7 (C-3), 69.6 (C-5), 67.8 (C- 6), 67.0 (C-4), 55.1 (OCH2C≡CH), 34.1 (CH-i-pr), 29.6 (CH-i-pr), 24.6, 24.5, 23.4 (6 × CH3); HRMS (ESI); m / z [M + Na]+calculated for C44H48O11NaS; found 819.2844. EXAMPLE 9 – Synthesis of compound 20 (G22)PROCEDURE2FOR SYNTHESIS OFSO3.PY

[0282] To a solution of pyridine (4 mL) in DCM (20 mL) at 0°C, chlorosulfonic acid (1.6 mL) was added dropwise and the mixture stirred for 30 min. The reaction mixture was then filtered and the precipitate was washed with ice cold water (3 × 20 mL), ice cold sat. NaHCO3 (2 × 10 mL), ice cold water (2 × 10 mL) (until the pH of the filtrate was 7), cold EtOH (2 × 20 mL), cold toluene (10 mL) and cold DCM (10 mL). The precipitated SO3.Py was then thoroughly dried under high vacuum and used within 24 h.GENERAL PROCEDURE 2 FOR CLICK REACTION

[0283] Sodium ascorbate (2 equiv.) and copper sulfate pentahydrate (1 equiv.) were added to a mixture of azide analogue (1 equiv.) and alkyne analogue (1 equiv. per N3) in 1,4-dioxane / H2O (3:1). The reaction mixture was then stirred at r.t. for 18 h and filtered over a pad of celite. The filtrate was concentrated under reduced pressure and the crude material was dissolved in EtOAc. The organic layer was washed with 1M HCl, sat. NaHCO3, dried (MgSO4) and concentrated under reduced pressure. The crude material obtained was purified by flash column chromatography on silica gel to obtain the desired compound. GENERAL PROCEDURE2FOR ACETATE AND BENZOYL ESTER HYDROLYSIS

[0284] A solution of 30% aq. NH3 (3-5 mL) and oligosaccharide in methanol (20 mL) was stirred at r.t. for 48 h. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in ultra-pure water (5-10 mL) and washed with EtOAc (5 × 10 mL). The aqueous layer was concentrated to obtain the pure compound. GENERAL PROCEDURE 2 FOR SULFATION

[0285] Freshly prepared SO3.Py (10 equiv. per OH) complex was added to a solution of the starting material in dry DMF (10 mL) kept under nitrogen atmosphere. The reaction mixture was stirred at r.t. for 2 days and made basic using 5 M NaOH (2 equiv. per SO3.Py). The mixture was then concentrated under reduced pressure and the crude material was dissolved in ultra-pure water (10-20 mL) and dialyzed according to the general procedure. GENERAL PROCEDURE 2 FOR DIALYSIS

[0286] Commercially available Cellulose membrane dialysis tubing with MWCO of 0.5 kD, 1kD and 2 kD were used for dialysis. The dialysis tubing was washed with milliQ water before use (approximately 5-10 mins of washing). One end of the dialysis tube was knotted and the sample was loaded into the tube. The tube was then closed using a clip, leaving little room for bubbles. A 3 L flask equipped with a stirrer bar was filled with milliQ water and placed on a magnetic stirring plate at room temperature. The stirring was set such that the dialysis bag slowly float around the top of the solution in the flask. After 2 h., the water was replaced with fresh milliQ water and dialysis continued for 2 days with the dialysis water being changed after every 18 h. The dialysis bag was then removed from the flask and the content of the bag was collected and freeze dried.SYNTHESIS OF OCTYL 2,3,4,6-TETRA-O-ACETYL-ALPHA-D-MANNOPYRANOSIDE (COMPOUND 13)

[0287] Octanol (4.0 mL, 25.5 mmol) was added to a stirred solution of 1,2,3,4,6-penta-O-acetyl-D-mannopyranose 3 (prepared according to Example 3) (5.6 g, 14.3 mmol) in dry DCM (100 mL). The mixture was cooled to 0°C and Boron trifluoride diethyl etherate (BF3.OEt2) (16.0 mL, 112.0 mmol) was added dropwise. The resulting mixture was stirred for 15 min, brought to r.t., and the stirring was continued for 24 h. The reaction mixture was diluted with DCM (100 mL) and poured into ice-cold sat. NaHCO3(100 mL) solution. The resulting mixture was stirred until bubbling seized. The organic phase was then separated and washed with (3 × 50 mL) sat. NaHCO3, water (100 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was then dissolved in MeOH (50 mL) and a catalytic amount of sodium was added to the mixture. The reaction was stirred at r.t. for 2 hours and neutralized with pre-washed acidic ion exchange resin (IR-120 H+), filtered and concentrated under reduced pressure. The crude material was purified by flash column chromatography (EtOAc / MeOH 3:1) to obtain 13 (2.5 g, 60%) as colorless oil. SYNTHESIS OF OCTYL 2,3,4-TRI-O-ACETYL-6-2,4,6-TRIISOPROPYLBENZENE SULFONYL- ALPHA-D-MANNOPYRANOSIDE (COMPOUND 14)

[0288] The crude material from above 13 (880 mg, 3.00 mmol) was dissolved in anhydrous pyridine (50 mL) and cooled to 0°C. 2,4,6-triisopropylbenzene sulfonyl chloride (1.18 g, 3.9 mmol) was added to the reaction mixture and allowed to warm up to r.t., and stirred for 18 h. The reaction mixture was then cooled to 0°C and acetic anhydride (2 mL) was added and stirred at r.t. for 24 h. The reaction mixture was concentrated under reduced pressure by co-evaporating the pyridine with toluene. The crude residue obtained was dissolved in EtOAc (100 mL) and washed with 1 M HCl (2 × 50 mL), sat. NaHCO3 (50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (Pet. Sp. / EtOAc 3:1) onsilica gel to afford the mannopyranoside 14 (1.7 g, 89%) as a colorless oil.1H NMR (CDCl3, 400 MHz): 7.18 (s, 2H, Ar-OTPS), 5.33 (dd, 1H, J2,3 = 3.5 Hz, J3,4 = 10.0 Hz, H- 3), 5.19 (dd, 1H, J1,2 = 1.7 Hz, J2,3 = 3.5 Hz, H-2), 5.11 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H- 4), 4.72 (d, 1H, J1,2= 1.7 Hz, H-1), 4.17-4.05 (m, 5H, H-5), 3.69-3.62 (m, 1H, H-6a), 3.41-3.33 (m, 1H, H-6b), 2.91 (h, 1H, J = 6.9 Hz, J = 13.7 Hz, J = 20.1 Hz, CH-i-pr), 2.09 (s, 3H, CH3), 1.98 (s, 3H, CH3), 1.97 (s, 3H, CH3), 1.67-0.69 (m, 36H, 7 × CH2, CH3, OCH3);13C NMR (CDCl3, 100 MHz): 170.0, 169.8 (×2), 153.8, 150.9, 129.2, 123.7, 97.2 (C-1), 69.7 (C-2), 67.0 (C-3), 68.6 (C-5), 68.5 (C-6), 67.7, 66.7 (C-4), 34.2, 31.8, 29.7, 29.6, 29.3, 29.2, 29.1, 26.0, 24.7, 24.6, 23.5, 22.6, 20.8, 20.6, 20.5, 14.1. SYNTHESIS OF OCTYL 2,3,4-TRI-O-ACETYL-6-AZIDO-ALPHA-D-MANNOPYRANOSIDE (COMPOUND 15)

[0289] To a solution of 14 (2.5 g, 3.7 mmol) in dry DMF (20 mL), NaN3 (800 mg, 20 mmol) was added and the mixture was stirred at 60°C for 24 h. The reaction mixture was then decanted and the residue left in the flask was washed with EtOAc (3 × 5 mL). The combined organic layer was then concentrated under reduced pressure. The crude material was dissolved in EtOAc (100 mL) and washed with 1M HCl (2 × 50 mL), sat. NaHCO3 (50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (Pet. Sp. / EtOAc 1:1) to obtain the azide 15 (quant.) as colorless oil.1H NMR (CDCl3, 400 MHz): 5.32 (dd, 1H, J = 3.5 Hz, J = 10.0 Hz, H-3), 5.23-5.15 (m, 2H, H-2, H-4), 4.79 (br-s, 1H, H-1), 3.96-3.88 (m, 1H, J = 2.5 Hz, J = 6.9 Hz, J = 9.6 Hz, H-5), 3.73-3.65 (m, 1H, J = 6.6 Hz, J = 9.4 Hz), 3.48-3.40 (m, 1H, J = 6.5 Hz, J = 9.4 Hz), 3.34 (dd, 1H, J = 6.7 Hz, J = 13.2 Hz, H- 6a), 3.24 (dd, 1H, J = 2.3 Hz, J = 13.1 Hz, H-6b), 2.13 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.96 (s, 3H, CH3), 1.67-0.71 (m, 18H, 7 × CH2, CH3);13C NMR (CDCl3, 100 MHz): 171.0, 170.0, 169.8, 97.3, 69.9, 69.6, 68.9, 68.6, 67.3, 60.3, 51.1, 31.7, 29.2, 29.1, 26.0, 22.6, 20.9, 20.8, 20.6, 14.1; HRMS (ESI); m / z [M + Na]+calculated for C20H33O8N3Na; found 466.2168.SYNTHESIS OF COMPOUND 16

[0290] Click reaction of 12 (prepared according to Example 8) (2.5 g, 3.10 mmol) and mannose azide 15 (2.0 g, 3.10 mmol) via general procedure 2 gave the disaccharide as a glassy solid. To a solution of the disaccharide in dry DMF (20 mL), sodium azide (500 mg, 7.40 mmol) was added and the mixture was stirred at 60°C under a nitrogen atmosphere for 18 h. The reaction mixture was then concentrated under reduced pressure and the crude material obtained was suspended in EtOAc (75 mL). The organic layer was washed with HCl (2 × 75 mL), sat. NaHCO3, dried (MgSO4) and concentrated. The crude material was then purified by flash column chromatography to obtain 16 (700 mg, 19%).1H NMR (CDCl3, 400 MHz): 8.12-8.06 (m, 2H, Ar-H), 7.98- 7.91 (m, 2H, Ar-H), 7.85 (s, 1H, H-9), 7.82-7.77 (m, 2H, Ar-H), 7.66-7.59 (m, 1H, Ar- H), 7.55-7.47 (m, 3H, Ar-H), 7.46-7.35 (m, 3H, Ar-H), 7.29-7.22 (m, 2H, Ar-H), 5.93- 5.86 (m, 1H, H-4), 5.83 (dd, 1H, J2,3 = 3.2 Hz, J3,4 = 10.0 Hz, H-3), 5.67 (dd, 1H, J1,2 = 1.7 Hz, J2,3 = 3.2 Hz, H-2), 5.37 (dd, 1H, J2’,3’ = 3.5 Hz, J3’,4’ =10.0 Hz, H-3’), 5.24 (dd, 1H, = 1.8 Hz, J2’,3’ =3.4 Hz, H-2’), 5.21 (d, 1H, J1’,2’ = 1.7 Hz, H-1’), 5.17 (t, 1H, J3’,4’= J4’,5’ = 10.0 Hz, H-4’), 5.04, 4.82 (ABq, 2H, J = 12.2 Hz, H-7), 4.77 (d, 1H, J1,2 = 1.6 Hz, H-1), 4.67 (dd, 1H, J5’,6’a = 2.4 Hz, J6’a,6’b = 14.3 Hz, H-6’a), 4.43 (dd, 1H, J5’,6’b = 9.0 Hz, J6’a, 6’b = 14.3 Hz, H-6’b), 4.37-4.31 (m, 1H, H-5), 4.19 (ddd, 1H, J5’,6’a = 2.3 Hz, J6’a, 6’b = 9.2 Hz, J = 12.0 Hz, H-5’), 3.52 (d, 2H, J = 4.4 Hz, H-6), 3.23 (dd, 2H, J = 1.5 Hz, J = 6.5 Hz, J = 8.1 Hz, H-7’), 2.17 (s, 3H, OCH3), 2.13 (s, 3H, OCH3), 1.99 (s, 3H, OCH2(CH2)6CH3), 1.48-1.37 (m, 2H, OCH2(CH2)6CH3), 1.27-1.14 (m, 8H, OCH2(CH2)6CH3), 1.13-1.07 (m, 2H, OCH2(CH2)6CH3), 0.86 (t, 3H, J = 6.8 Hz, OCH2(CH2)6CH3);13C NMR (CDCl3, 100 MHz): 171.1, 170.2, 169.9, 169.7, 165.5, 165.4 (×2), 143.4 (C-8), 133.6 (×2), 133.2, 129.8 (×2), 129.7, 129.1, 128.9, 128.7, 128.6, 128.5, 128.3, 124.7 (C-9), 97.4 (C-1’), 96.9 (C-1), 70.6 (C-5), 70.2 (C-2), 69.6 (C-3), 69.6 (C-2’), 69.1 (C-5’), 68.8 (C-3’), 68.5 (OCH2(CH2)6CH3), 67.7 (C-4), 67.5 (C-4’), 61.3 (C-7), 51.2 (C-6), 51.1 (C-6’), 31.7 (OCH2(CH2)6CH3), 29.2 (OCH2(CH2)6CH3), 29.1 (×2) (OCH2(CH2)6CH3), 26.0 (OCH2(CH2)6CH3), 21.0 (OCH2(CH2)6CH3), 20.8 (×2) (2 × OCH3), 20.6 (OCH3), 14.2 (OCH2(CH2)6CH3), 14.0 (OCH2(CH2)6CH3).SYNTHESIS OF COMPOUND 17

[0291] Click reaction of disaccharide 16 (700 mg, 0.60 mmol) and 5-hexyn-1-ol (0.09 mL, 0.90 mmol) via general procedure 2 gave the disaccharide as a glassy solid. To a solution of the crude material in anhydrous DCM (20 mL), triethylamine (0.6 mL, 4.5 mmol) and methanesulfonyl chloride (0.07 mL, 0.90 mmol) were added and stirred at r.t. for 18 h. The reaction mixture was washed with 1 M HCl (2 × 30 mL), sat. NaHCO3 (30 mL), dried (MgSO4) and concentrated under reduced pressure. To a solution of the crude material in anhydrous DMF (20 mL), NaN3(100 mg, 1.7 mmol) was added and stirred at 60°C for 18 h. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in EtOAc (100 mL) and washed with 1 M HCl (50 mL), sat. NaHCO3 (50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (1.5:1 EtOAc / Pet. Sp. to EtOAc) to obtain the azide 17 (370 mg, 58%).1H NMR (CDCl3, 400 MHz): 8.04-7.92 (m, 4H, Ar-H), 7.79-7.74 (m, 3H, Ar-H, H-9), 7.66-7.56 (m, 2H, Ar-H, H-10), 7.55-7.44 (m, 3H, Ar-H), 7.44-7.34 (m, 3H, Ar-H), 7.26-7.19 (m, 2H, Ar-H), 5.82 (dd, 1H, J2’,3’ = 3.4 Hz, J3’,4’ = 10.0 Hz, H-3’), 5.73 (t, 1H, J3’,4’= J4’,5’= 9.7 Hz, H-4’), 5.59 (dd, 1H, J2’,3’= 1.7 Hz, J1’,2’= 3.3 Hz, H-2’), 5.35 (dd, 1H, J2,3 = 3.5 Hz, J3,4 = 10.0 Hz, H-3), 5.23 (dd, 1H, J1,2 = 1.7 Hz, J2,3 = 3.5 Hz, H-2), 5.15 (d, 1H, J1’,2’ = 1.7 Hz, H-1’), 5.14 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 4.77 (d, 1H, J1,2 = 1.6 Hz), 4.76-4.67 (m, 1H, H-6’a ), 4.66-4.55 (m, 3H, H- 6’b, H-6a, H-5’), 4.60, 4.51 (ABq, 2H, H-7), 4.42 (dd, 1H, J5,6b = 8.2 Hz, J6a,6b = 14.4 Hz, H-6b), 4.22-4.15 (m, 1H, H-5), 3.27-3.19 (m, 4H, OCH2(CH2)6CH3, triazole- (CH2)3CH2N3), 2.78-2.65 (m, 2H, triazole-(CH2)3CH2N3), 2.15 (s, 3H, OCH3), 2.11 (s, 3H, OCH3), 1.98 (s, 3H, OCH3), 1.76-1.65 (m, 2H, triazole-(CH2)3CH2N3), 1.65-1.54 (m, 2H, triazole-(CH2)3CH2N3), 1.46-1.34 (m, 2H, OCH2(CH2)6CH3), 1.21-1.10 (m, 8H, OCH2(CH2)6CH3), 0.83 (t, 3H, OCH2(CH2)6CH3);13C NMR (CDCl3, 100 MHz): 170.0, 169.9, 169.7, 165.7, 165.2 (×2), 147.5 (C-9), 143.0 (C-11), 133.7, 133.6, 133.2, 129.8 (×2), 129.6, 129.0, 128.7, 128.6, 128.5, 128.2, 124.7 (C-9), 122.5 (C-10), 97.3 (C-1), 96.5 (C-1’), 70.2 (C-2’), 69.6 (C-5’), 69.5 (C-3’, C-2), 68.9 (C-5), 68.8 (C-3), 68.4 (OCH2(CH2)6CH3), 67.9 (C-4’), 67.6 (C-4), 60.7 (C-7), 51.0 (C-6, triazole-(CH2)3CH2N3), 50.9 (C-6’), 31.7 (OCH2(CH2)6CH3), 29.2 (OCH2(CH2)6CH3), 29.1 (OCH2(CH2)6CH3) , 28.2(triazole-(CH2)3CH2N3), 26.4 (triazole-(CH2)3CH2N3), 26.0 (OCH2(CH2)6CH3), 25.0 (triazole-(CH2)3CH2N3), 22.5, 20.8 (OCH3), 20.7 (OCH3), 20.6 (OCH3), 14.0 (OCH2(CH2)6CH3). SYNTHESIS OF COMPOUND 18

[0292] Click reaction of azide 17 (130 mg, 0.12 mmol) and propargyl maltotriose 11 (prepared according to Example 7) (120 mg, 0.10 mmol) via general procedure 2 gave the oligosaccharide 18 (120 mg, 53%) as a glassy solid;1H NMR (CDCl3, 400 MHz): δ = 8.04-7.91 (m, 4H), 7.81-7.74 (m, 3H), 7.68-7.59 (m, 2H), 7.57- 7.46 (m, 4H), 7.46-7.35 (m, 3H), 7.26-7.20 (m, 2H), 5.83 (dd, 1H, J = 3.3 Hz, J = 10.0 Hz), 5.72 (m, 1H, J = 9.8 Hz), 5.60 (dd, 1H, J = 1.7 Hz, J = 3.3 Hz), 5.43-5.30 (m, 4H), 5.29-5.20 (m, 3H), 5.17-5.02 (m, 3H), 4.95-4.39 (m, 17H), 4.39-4.11 (m, 6H), 4.05 (dd, 1H, J = 2.2 Hz, J = 12.4 Hz), 4.01-3.87 (m, 4H), 3.79-3.70 (m, 1H), 3.24 (t, 2H, J = 6.4 Hz), 2.81-2.71 (m, 2H), 2.19-1.92 (10 × s, 30H), 1.76-1.64 (m, 2H), 1.47-1.36 (m, 2H), 1.30-1.11 (m, 10H), 0.84 (t, 3H, J = 6.8 Hz);13C NMR (CDCl3, 100 MHz): δ = 170.6 (×2), 170.5, 170.4, 170.3, 170.1, 170.0, 169.9, 169.8, 169.7 (×2), 169.6, 169.4, 165.7, 165.3, 165.2, 146.9, 143.8, 143.0, 133.8, 133.7, 133.3, 129.9, 129.8, 129.7, 129.0, 128.8, 128.7, 128.5 (×2), 128.3, 124.8, 123.0, 122.9, 99.5, 97.3, 96.5, 95.7, 95.6, 77.2, 75.2, 73.7, 72.5, 72.3, 72.0, 71.7, 70.4, 70.2, 70.0, 69.6, 69.5, 69.4, 69.0, 68.9, 68.8, 68.5, 67.9, 67.6, 62.9, 62.8, 62.3, 61.4, 60.8, 51.1 (×2), 50.0, 31.8, 29.5, 29.2, 29.1, 26.1, 26.0, 24.6, 22.6, 20.9, 20.8 (×2), 20.6, 20.5 (×2), 14.1. SYNTHESIS OF COMPOUND 19

[0293] Acetate and benzoyl ester hydrolysis of compound 18 (120 mg, 0.05 mmol) according to general procedure 2 gave the oligosaccharide 19 (47 mg, 73%)1H NMR (D2O, 400 MHz): δ = 7.93 (s, 1H), 7.86 (s, 1H), 7.80 (s, 1H), 5.32 (t, 2H, J = 4.2 Hz), 4.93-4.74 (m, 5H), 4.54-4.37 (m, 3H), 4.33 (t, 2H, J = 7.0 Hz), 4.21, 4.14 (ABq, 2H, J = 12.1 Hz), 3.95-3.48 (m, 26H), 3.37 (t, 1H, J = 9.6 Hz), 3.31-3.19 (m, 2H), 2.99-2.90 (m, 1H), 2.69 (t, 2H, J = 7.4 Hz), 1.86-1.76 (m, 2H), 1.61-1.50 (m, 2H), 1.29-0.83 (m, 12H), 0.79 (t, 3H, J = 7.0 Hz);13C NMR (D2O, 100 MHz): δ = 147.7, 143.4, 142.8, 125.9, 125.1, 124.2, 101.3, 99.9, 99.8, 99.6, 99.0, 77.2, 77.0, 76.1, 74.6, 73.3, 72.9 (×2), 72.7, 71.8 (×2), 71.5, 71.2, 70.6, 70.5, 70.0, 69.8, 69.3, 68.1 (×2), 67.9, 61.9, 60.7, 60.5, 58.9, 51.3, 51.1, 50.0, 31.0, 28.6, 28.4, 28.3, 28.2, 25.5, 25.3, 23.8, 22.1, 13.5. SYNTHESIS OF COMPOUND 20

[0294] Sulfation of the deprotected oligosaccharide 19 (55 mg, 0.04 mmol) according to general procedure 2 followed by dialysis gave the oligosaccharide 20 (30 mg, 26%) as a white powder;1H NMR (D2O, 400 MHz): δ = 8.16 (s, 1H), 8.02 (s, 1H), 8.00 (s, 1H), 5.75-5.66 (m, 1H), 5.64-5.55 (m, 1H), 8.26 (s, 1H), 5.23-4.88 (m, 10H), 4.88-4.66 (m), 4.66-4.31 (m, 15H), 4.30-4.12 (m, 5H), 4.06 (t, 1H, J = 10.0 Hz), 3.45- 3.36 (m, 1H), 2.06-1.90 (m, 2H), 1.78-1.62 (m, 2H), 1.44-0.96 (m, 10H), 0.89 (t, 3H, J = 7.0 Hz);13C NMR (CDCl3, 100 MHz): δ = 125.9, 125.6, 124.3, 99.4, 97.1, 96.3, 94.3, 93.6, 76.3, 75.5, 75.2, 74.7, 73.7, 73.5, 73.0, 72.7, 72.6, 71.6, 71.4, 70.7, 70.6, 69.8, 67.8, 66.5, 65.9, 62.1, 59.8, 51.1, 50.9, 50.1, 31.0, 28.8, 28.4, 28.2, 28.1, 25.6, 25.2, 24.0, 22.1, 13.5. EXAMPLE 10 – Synthesis of compound 25 (G19).

[0296] To a solution of pyridine (4 mL) in DCM (20 mL) at 0°C, chlorosulfonic acid (1.6 mL) was added dropwise and the mixture stirred for 30 min. The reaction mixture was then filtered and the precipitate was washed with ice cold water (3 × 20 mL), ice cold sat. NaHCO3 (2 × 10 mL), ice cold water (2 × 10 mL) (until the pH of the filtrate was 7), cold EtOH (2 × 20 mL), cold toluene (10 mL) and cold DCM (10 mL). The precipitated SO3.Py was then thoroughly dried under high vacuum and used within 24 h. GENERAL PROCEDURE 3 FOR CLICK REACTION

[0297] Sodium ascorbate (2 equiv.) and copper sulfate pentahydrate (1 equiv.) were added to a mixture of azide analogue (1 equiv.) and alkyne analogue (1 equiv. per N3) in 1,4-dioxane / H2O (3:1). The reaction mixture was then stirred at r.t. for 18 h. and filtered over a pad of celite. The filtrate was concentrated under reduced pressure andthe crude material was dissolved in EtOAc. The organic layer was washed with 1M HCl, sat. NaHCO3, dried (MgSO4) and concentrated under reduced pressure. The crude material obtained was purified by flash column chromatography on silica gel to obtain the desired compound. GENERAL PROCEDURE 3 FOR ACETATE ESTER HYDROLYSIS

[0298] A solution of 30% aq. NH3 (3-5 mL) and oligosaccharide in methanol (20 mL) was stirred at r.t. for 48 h. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in ultra-pure water (5-10 mL) and washed with EtOAc (5 × 10 mL). The aqueous layer was concentrated to obtain the pure compound. GENERAL PROCEDURE 3 FOR SULFATION

[0299] Freshly prepared SO3.Py (10 equiv. per OH) complex was added to a solution of the starting material in dry DMF (10 mL) kept under nitrogen atmosphere. The reaction mixture was stirred at r.t. for 2 days and made basic using 5 M NaOH (2 equiv. per SO3.Py). The mixture was then concentrated under reduced pressure and the crude material was dissolved in ultra-pure water (10-20 mL) and dialyzed according to the general procedure. GENERAL PROCEDURE 3 FOR DIALYSIS

[0300] Commercially available Cellulose membrane dialysis tubing with MWCO of 0.5 kD, 1kD and 2 kD were used for dialysis. The dialysis tubing was washed with milliQ water before use (approximately 5-10 mins of washing). One end of the dialysis tube was knotted and the sample was loaded into the tube. The tube was then closed using a clip, leaving little room for bubbles. A 3 L flask equipped with a stirrer bar was filled with milliQ water and placed on a magnetic stirring plate at room temperature. The stirring was set such that the dialysis bag slowly float around the top of the solution in the flask. After 2 h., the water was replaced with fresh milliQ water and dialysis continued for 2 days with the dialysis water being changed after every 18 h. The dialysis bag was then removed from the flask and the content of the bag was collected and freeze dried. SYNTHESIS OF COMPOUND 21

[0301] Click reaction of sucralose azide 2 (prepared according to Example 2) (2.05 g, 3.33 mmol) and 4-pentyn-1-ol (430 mg, 5.1 mmol) via general procedure 3 led to the compound 21 (2.00 g, 86%).1H NMR (CDCl3, 400 MHz): δ = 7.47 (s, 1H, H-7’), 5.68-5.64 (m, 2H, H-1, H-3’), 5.36 (t, 1H, J = 7.2 Hz, H-4), 5.30-5.29 (m, 2H, H-4’, H- 3), 4.76 (A part of ABX, 1H, J5,6a = 3.6 Hz, J6a,6b = 14.4 Hz, H-6a), 4.63 (B part of ABX, J5,6b = 8.7 Hz, J6a,6b = 14.4 Hz, H-6b), 4.60-4.54 (m, 2H, H-2, H-5’), 4.41-4.34 (m, 1H,H- 5), 4.28 (A part of ABX, J5’,6’a = 4.9 Hz, J6’a,6’b = 11.8 Hz, H-6’a), 4.21 (B part of ABX, J5’,6’b = 6.7 Hz, J6’a,6’b = 11.8 Hz, H-6’b), 3.67 (t, 2H, J10’,11’ = 6.1 Hz, H-11’), 3.61, 3.47 (ABq, 2H, J = 12.0 Hz, H-1’), 2.82 (t, 2H, J9’,10’ = 7.3 Hz, H-9’), 2.11 (s, 3H, OCH3), 2.10 (s, 3H, OCH3), 2.07 (s, 6H, 2 × OCH3), 2.04 (s, 3H, OCH3), 1.96-1.87 (m, 2H, H-10’);13C NMR (CDCl3, 100 MHz): δ = 170.4, 170.2, 170.2 (×2), 169.6, 147.5 (C-8’), 122.6 (C- 7’), 103.9 (C-2’), 90.4 (C-1), 79.4 (C-5), 75.3 (C-4), 75.2 (C-2’), 68.1, 67.7, 67.0, 63.8 (C-6’), 61.5 (C-11’), 58.9, 52.4 (C-6), 44.8 (C-9’), 31.7 (C-10’), 21.8, 20.7 (×2), 20.6 (OCH3), 20.5 (OCH3), 20.4 (OCH3). SYNTHESIS OF COMPOUND22

[0302] To a solution of the alcohol 21 (2.00 g, 2.86 mmol) in anhydrous DCM (20 mL), triethylamine (1.5 mL) and methanesulfonyl chloride (0.5 mL, 4.76 mmol) were added and stirred at r.t. for 18 h. The reaction mixture was washed with 1 M HCl (2 × 30 mL), sat. NaHCO3 (30 mL), dried (MgSO4) and concentrated under reduced pressure. To a solution of the crude material in anhydrous DMF (20 mL), NaN3 (304 mg, 4.76 mmol) was added and stirred at 60°C for 18 h. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in EtOAc (100 mL) and washed with 1 M HCl (50 mL), sat. NaHCO3(50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by flash column chromatography (1.5:1 EtOAc / Pet. Sp. to EtOAc) to obtain the azide 22 (1.24 g, 60%).1H NMR (CDCl3, 400 MHz): δ = 7.43 (s, 1H, H-7’), 5.65-5.61 (m, 2H, H-1, H-3’), 5.34 (t, 1H, J = 7.2 Hz, H-4), 5.29-5.25 (2H, H-3, H-4’), 4.74 (A part of ABX, 1H, J5,6a = 3.6 Hz, J6a,6b = 14.3 Hz, H-6a), 4.60 (B part of ABX, J5,6b = 8.8 Hz, J6a,6b = 14.4 Hz, H-6b), 4.56-4.51 (m, 2H, H- 2, H-5’), 4.38-4.31 (m, 1H,H-5), ), 4.25 (A part of ABX, J5’,6’a = 4.8 Hz, J6’a,6’b = 11.8 Hz, H-6’a), 4.17 (B part of ABX, J5’,6’b = 6.7 Hz, J6’a,6’b = 11.8 Hz, H-6’b), 3.58, 3.44 (ABq, 2H, J = 12.0 Hz, H-1’), 3.30 (t, 2H, J10’,11’ = 6.7 Hz, H-11’), 2.76 (t, 2H, J9’,10’ = 7.4 Hz, H-9’), 2.08 (s, 3H, OCH3), 2.07 (s, 3H, OCH3), 2.03 (s, 6H, 2 × OCH3), 2.01 (s, 3H, OCH3),1.98-1.91 (m, 2H, H-10’);13C NMR (CDCl3, 100 MHz): δ = 170.2, 169.9 (×3), 169.5, 146.5, 122.3, 103.8, 90.3, 79.4, 75.2, 75.1, 68.0, 67.6, 66.8, 63.7, 58.8, 52.2, 50.5, 44.8, 28.3, 22.4, 20.6 (×2), 20.4, 20.3. SYNTHESIS OF COMPOUND 23

[0303] Click reaction of the azide 22 (500 mg, 0.70 mmol) and propargyl maltotriose 11 (prepared according to Example 7) (700 mg, 0.70 mmol) via general procedure 3 gave the oligosaccharide 23 (700 mg, 59%) as a glassy solid;1H NMR (CDCl3, 400 MHz): δ = 7.57 (s, 1H), 7.47 (s, 1H), 5.67-5.60 (m, 2H), 5.36-5.21 (m, 6H), 5.21-5.12 (m, 2H), 4.97 (t, 1H, J = 10.0 Hz), 4.86-4.68 (m, 5H), 4.68-4.49 (m, 5H), 4.46-4.28 (m, 5H), 4.23 (dd, 2H, J = 4.4 Hz, J = 12.0 Hz), 4.19-4.07 (m, 3H), 3.96 (dd, 1H, J = 2.3 Hz, J = 12.4 Hz), 3.93-3.81 (m, 4H), 3.73-3.62 (m, 1H), 3.57, 3.47 (ABq, 2H, J = 12.1 Hz), 2.73-2.57 (m, 2H), 2.24 (t, 2H, J = 6.7 Hz), 2.08-1.87 (15 × s, 45H);13C NMR (CDCl3, 100 MHz): δ = 170.8, 170.4, 170.3 (×2), 170.1 (×2), 169.9, 169.8, 169.6, 169.5, 169.4 (×2), 169.2, 147.9, 145.7, 143.8, 123.0, 122.8, 103.9, 99.2, 95.5, 95.4, 90.4, 79.4, 75.2, 75.0, 73.6, 72.4, 72.0, 71.8, 71.5, 70.2, 69.8, 69.1, 68.7, 68.3, 68.0, 67.7, 67.6, 66.7, 63.8, 62.7, 62.6, 62.1, 61.2, 58.8, 52.3, 48.9, 44.6, 29.4, 21.8, 20.8, 20.7, 20.6 (×2), 20.5 (×2), 20.4, 20.3 (×2), 20.2. SYNTHESIS OF COMPOUND24according to general procedure 3 gave the oligosaccharide 24 (412 mg, 93%);1H NMR (D2O, 400 MHz): δ = 8.02 (s, 1H), 7.79 (s, 1H), 5.43-5.38 (m, 3H), 4.98, 4.85 (ABq, 2H, J = 12.6 Hz), 4.68 (d, 1H, J = 7.9 Hz), 4.54 (d, 1H, J = 3.8 Hz), 4.51-4.40 (m, 4H), 4.24-4.15 (m, 2H), 4.04-3.55 (m, 21H), 3.44 (t, 1H, J = 9.3 Hz), 3.37 (dd, 1H, J = 1.3 Hz, J = 9.4 Hz, 1H), 2.73 (t, 2H, J = 7.1 Hz), 2.31 (p, 2H, J = 7.2 Hz, J = 13.8 Hz);13C NMR (D2O, 100 MHz): δ = 177.3, 146.6, 143.5, 125.2, 124.1, 103.4, 101.9, 101.4, 99.8,99.6, 99.3, 92.4, 79.5, 78.9, 77.1, 76.9, 76.1, 75.6, 74.8, 74.6, 73.3, 72.9 (×2), 72.7, 71.8, 71.5, 71.2, 70.6, 69.3, 68.0, 67.5, 63.1, 62.0, 61.8, 60.7, 60.5, 52.1, 49.6, 43.8, 28.7, 21.6. SYNTHESIS OF COMPOUND 25according to general procedure 3 followed by dialysis gave the pentamer 25 (102 mg, 17%) as a white powder;1H NMR (D2O, 400 MHz): δ = 8.21 (s, 1H), 7.98 (s, 1H), 5.83 (d, 1H, J = 3.4 Hz), 5.76-5.69 (m, 1H), 5.63 (d, 1H, J = 2.9 Hz), 5.42 (d, 1H, J = 7.4 Hz), 5.21-4.87 (m, 11H), 4.93-4.61 (m, 7H), 4.62-4.14 (m, 17H), 4.04, 3.95 (ABq, 2H, J = 12.1 Hz), 2.47-2.29 (m, 2H);13C NMR (CDCl3, 100 MHz): δ = 125.7, 124.7, 103.6, 99.4, 94.4, 93.7, 90.9, 79.5 (×2), 78.3, 76.3, 76.1, 74.7, 73.6, 73.0, 72.6, 72.4, 71.8, 71.6, 71.4, 70.2, 69.8, 68.4, 67.8, 66.5, 66.0, 62.0, 60.3, 52.7, 49.7, 44.0, 29.0, 21.6. EXAMPLE 11 – Synthesis of compound 29 (G4)PROCEDURE4FOR SYNTHESIS OFSO3.PY

[0306] To a solution of pyridine (4 mL) in DCM (20 mL) at 0°C, chlorosulfonic acid (1.6 mL) was added dropwise and the mixture stirred for 30 min. The reaction mixture was then filtered and the precipitate was washed with ice cold water (3 × 20 mL), ice cold sat. NaHCO3 (2 × 10 mL), ice cold water (2 × 10 mL) (until the pH of the filtrate was 7), cold EtOH (2 × 20 mL), cold toluene (10 mL) and cold DCM (10 mL). The precipitated SO3.Py was then thoroughly dried under high vacuum and used within 24 h.GENERAL PROCEDURE 4 FOR SULFATION

[0307] Freshly prepared SO3.Py (10 equiv. per OH) complex was added to a solution of the starting material in dry DMF (10 mL) kept under nitrogen atmosphere. The reaction mixture was stirred at r.t. for 2 days. The DMF was then decanted from the reaction mixture and the precipitated material was dissolved in ultra-pure water (10 mL) and made basic using 5 M NaOH (pH = 9-11). The solution was then dialyzed according to the general procedure. GENERAL PROCEDURE 4 FOR DIALYSIS

[0308] Commercially available Cellulose membrane dialysis tubing with MWCO of 0.5 kD, 1kD and 2 kD were used for dialysis. The dialysis tubing was washed with milliQ water before use (approximately 5-10 mins of washing). One end of the dialysis tube was knotted and the sample was loaded into the tube. The tube was then closed using a clip, leaving little room for bubbles. A 3 L flask equipped with a stirrer bar was filled with milliQ water and placed on a magnetic stirring plate at room temperature. The stirring was set such that the dialysis bag slowly float around the top of the solution in the flask. After 2 h., the water was replaced with fresh milliQ water and dialysis continued for 2 days with the dialysis water being changed after every 18 h. The dialysis bag was then removed from the flask and the content of the bag was collected and freeze dried. GENERAL PROCEDURE 4 FOR ACETATE AND BENZOYL ESTER HYDROLYSIS

[0309] A solution of 30% aq. NH3 (3-5 mL) and oligosaccharide in methanol (20 mL) was stirred at r.t. for 48 h. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in ultra-pure water (5-10 mL) and washed with EtOAc (5 × 10 mL). The aqueous layer was concentrated to obtain the pure compound. GENERAL PROCEDURE 4 FOR CLICK REACTION CuSO4•5H2O, Na asorbate 18h R2

[0310] Sodium ascorbate (2 equiv.) and copper sulfate pentahydrate (1 equiv.) were added to a mixture of azide analogue (1 equiv.) and alkyne analogue (1 equiv. per N3) in 1,4-dioxane / H2O (3:1). The reaction mixture was then stirred at r.t. for 18 h. and filtered over a pad of celite. The filtrate was concentrated under reduced pressure and the crude material was dissolved in EtOAc. The organic layer was washed with 1M HCl, sat. NaHCO3, dried (MgSO4) and concentrated under reduced pressure. The crudematerial obtained was purified by flash column chromatography on silica gel to obtain the desired compound. SYNTHESIS OF ACETYLATED PROPARGYL ACARBOSE (COMPOUND 26)to a mixture of peracetate acarbose (0.6 g, 0.5 mmol) and propargyl alcohol (35 µL, 0.6 mmol) in dry DCM (20 mL) at 0°C. The mixture was then stirred at r.t. for 5 h. Saturated NaHCO3 (10 mL) was then added to the reaction mixture and stirred for a further 10 min. The organic layer was extracted, dried (MgSO4) and concentrated under reduced pressure. The crude material obtain was purified by flash column chromatography (3:1 EtOAc / Pet. Sp.) to obtain propargyl acarbose 26 (0.1 g, 17%) as a glassy solid.1H NMR (CDCl3, 400 MHz): δ = 5.95 (d, 1H, J = 5.3 Hz), 5.60-5.51 (m, 2H), 5.40-5.31 (m, 1H), 5.31-5.18 (m, 3H), 5.10 (t, 1H, J = 10.2 Hz), 4.92 (dd, 1H, J = 4.3 Hz, J = 10.0 Hz), 4.85-4.69 (m, 4H), 4.67-4.60 (m, 1H), 4.49 (dd, 1H, J = 2.9 Hz, J = 12.3 Hz), 4.47-4.34 (d, 2H), 4.33 (d, 2H, J = 2.3 Hz), 4.29 (dd, 1H, J = 4.0 Hz, J = 12.4 Hz), 4.20-4.14 (m, 1H), 3.99 (t, 1H, J = 9.3 Hz), 3.94-3.88 (m, 2H), 3.77-3.67 (m, 2H), 3.57-3.46 (m, 1H), 2.46 (t, 1H, J = 2.4 Hz), 2.39 (t, 1H, J = 9.9 Hz), 2.16, 2.13, 2.09, 2.04, 2.02, 2.01, 2.00, 1.97, 1.96 (s, OCH3) ppm;13C NMR (CDCl3, 100 MHz): δ = 171.0, 170.7, 170.6, 170.5, 170.3 (×2), 170.2, 169.9, 169.7, 169.6, 133.9, 128.0, 97.5, 95.8, 95.6, 78.0, 77.2, 75.5, 75.3, 73.3, 72.2 (×2), 71.8 (×2), 71.0, 70.9, 70.7, 70.5, 70.1, 69.8, 69.1, 63.0, 62.7, 62.2, 61.1, 55.8, 52.1, 20.8, 20.7, 20.6, 20.5 (×2), 18.1 ppm.SYNTHESIS OF TRIETHYLENE ETHER LINKED DIACARBOSE (COMPOUND 27)

[0312] Click reaction of propargyl acarbose 26 (350 mg, 0.30 mmol) and 1,2- bis(2-azidoethoxy)ethane (30 mg, 0.13 mmol) via general procedure 4 gave the diacarbose 27 (235 mg, 71%) as a solid;1H NMR (CDCl3, 400 MHz): δ = 7.62 (s, 2H), 5.93 (d, 2H, J = 5.2 Hz), 5.59-5.49 (m, 4H), 5.37-5.29 (m, 2H), 5.26-5.17 (m, 6H), 5.07 (t, 2H, J = 10.2 Hz), 4.93-4.86 (m, 4H), 4.83-4.58 (, 12H), 4.56-4.40 (m, 8H), 4.38- 4.22 (m, 4H), 4.19-4.11 (m, 2H), 4.00-3.79 (m. 10H), 3.74-3.65 (m, 4H), 3.54-3.44 (m, 4H), 2.36 (t, 2H, J = 10.0 Hz), 2.14 (s, 6H), 2.12 (s, 6H), 2.10 (s, 6H), 2.04-1.91 (m, 54H), 1.18 (d, 6H, J = 6.2 Hz);13C NMR (CDCl3, 100 MHz): δ = 171.0, 170.7, 170.6, 170.4, 170.3 (×2), 170.2, 170.0, 169.9, 169.7, 169.6, 143.8, 133.9, 128.0, 124.0, 99.44, 95.8, 95.6, 77.2, 75.3, 73.4, 72.2 (×2), 72.0, 71.9, 71.0, 70.9, 70.7, 70.5, 70.4, 70.1, 69.8, 69.4, 69.1, 63.0, 62.9, 62.7, 62.2, 61.1, 52.1, 50.2, 20.9, 20.8, 20.7, 20.6 (×2), 20.5, 18.1. SYNTHESIS OF DIACARBOSE(COMPOUND28)

[0313] Acetate hydrolysis of compound 27 (0.24 g, 94 µmol) according to general procedure 4 gave the diacarbose compound 28 (0.15 mg, 99%).1H NMR (D2O, 400 MHz): δ = 8.00 (s, 1H), 5.86-5.82 (m, 1H), 5.32 (d, 1H, J = 3.8 Hz), 5.25 (d, 1H, J = 3.4 Hz), 4.92, 4.80 (ABquat. 2H), 4.56-4.47 (m, 2H), 4.17, 4.06 (ABquat., 2H, J = 13.7 Hz), 3.98 (d, 1H, J = 6.9 Hz), 3.91-3.43 (m, 22H), 3.26 (dd, 1H, J = 8.0 Hz, J = 9.4 Hz), 2.41 (t, 1H, J = 9.5 Hz), 1.28 (d, 3H, J = 6.3 Hz);13C NMR (D2O, 100 MHz): δ = 143.5, 138.9, 125.7, 123.8, 101.3, 100.0, 99.5, 77.1, 77.0, 74.6, 73.3, 73.0, 72.9 (×2), 72.7, 71.4, 71.2 (×2), 70.8, 69.6, 68.7, 64.9, 61.9, 61.6, 60.7, 60.5, 56.0, 50.1, 17.3. SYNTHESIS OF SULFATED DIACARBOSE (COMPOUND 29)

[0314] Sulfation of the deprotected octomer 28 (50 mg, 0.03 mmol) according to general procedure 4 followed by dialysis gave 29 (60 mg, 53%) as a white powder;1H NMR (D2O, 400 MHz): δ = 8.18 (s, 2H), 6.14 (s, 2H), 5.67 (d, 2H, J = 3.1 Hz), 5.59 (d, 2H, J = 2.7 Hz), 5.57-5.52 (m, 2H), 5.22-5.14 (m, 2H), 5.14-5.55 (m), 4.55-4.38 (m, 6H), 4.37-4.18 (m, 8H), 4.18-4.04 (m, 4H), 4.02-3.90 (m 4H), 3.74-3.57 (m, 4H), 3.45- 3.27 (m, 2H), 1.54 (d, 6H, J = 6.0 Hz). EXAMPLE 12 – Synthesis of compound 30 (G17)

[0315] Compound 30 (G17) was prepared in accordance with the procedure disclosed in WO 2018 / 068090 A1, the entire content of which is incorporated herein.EXAMPLE 13 – Inhibition of interaction between heparin and SARS-CoV-2 spike protein and the receptor binding domain (RBD) thereof

[0316] The ability of the compounds to inhibit the interaction between heparin and the SARS-CoV-2 spike protein and the receptor domain (RBD) thereof wasassessed using surface plasmon resonance (SPR). The optical phenomenon of SPR is used to monitor physical interactions between molecules. Passing a solution of a potential protein ligand (e.g. viral proteins like the spike protein from SARS-CoV-2, or the RBD of this spike protein) over a sensor surface to which a target (e.g. heparin) is coupled monitors the real-time binding of protein ligands to the immobilized target. Detection is achieved by measuring refractive index changes very close to the sensor surface. When the refractive index is altered, the angle at which plasmon resonance occurs changes and this change directly correlates with the amount of protein interacting with the surface. A BIAcore T200 is conveniently used. It is very sensitive and its microfluidics ensures that only small amounts of material are required.

[0317] For the present experiment, biotinylated heparin was immobilized on the biosensor chip. Biotinylation occurs via amino groups, or reducing termini modified with ammonia by reductive amination, using sulfo-NHS-biotin (refer to, for example, Osmond et al. (2002) Anal Biochem, 310(2):199-207). Solutions containing potential protein ligands of interest are injected over the sensor chip surface, and the binding is measured in real time (refer to, for example, Fernig (2001) In: Proteoglycan protocols, Ed. R.V. Iozzo, Humana Press, Totowa, NJ, USA).

[0318] To screen the sulfated glycoconjugates a competitive inhibition assay was used. In this case the test compound (G24, G17, G4, G19 or G22, made in accordance with Examples 1-12) was mixed with the protein of interest (e.g. full-length spike protein or RBD thereof) in the fluid phase prior to the passing of this mixture over the biosensor chip surface that has been coupled with heparin. If the test compound binds to the protein in a manner that inhibits the protein from then binding to heparin, a reduced signal will be detected from that in the absence of the test compound. A titration of the test compound whilst retaining the protein concentration constant allows the IC50 to be calculated, which can then be used to compare the various test compound for their inhibition of protein binding. The concentration of protein used in this assay varied according to the protein being examined, and was determined based on the signal achieved in the absence of the test compound. The concentration used for the RBD of spike protein was 120 nM and the full length spike protein was 95 nM.

[0319] The results are shown in Table 1. TABLE 1: INHIBITION OF THE INTERACTION BETWEEN FULL LENGTH SARS-COV-2 SPIKE PROTEIN AND THE RBD THEREOF. Full-length spike protein (95 RBD (120 nM) nM) 1EXAMPLE 14 – Ability of G17, G22 and G24 to inhibit RBD binding to ACE2 expressing Calu-3 cells

[0320] The human adenocarcinoma cell line, Calu-3, which express the human ACE2 receptor was used. Calu-3 cells (25 x 104) in Eagle’s minimal essential medium (MEM) containing 10% foetal bovine serum were seeded into the wells of a 24-well plate that contained collagen coated coverslips. Cells were allowed to adhere to the coverslip for approximately 1 h. and then the volume of medium in the well was increased to 1 mL. Culturing continued for 5 days to ensure a good covering of cells over the coverslip. Recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) with a C-terminal His tag (9.4 µg / mL) was mixed with either heparin (100 µg / mL), or the test compound (G17, G22 or G24, made in accordance with Examples 6, 9 and 12; 100 µg / mL), and incubated at room temperature for 45 min. All concentrations are the final concentration and the base medium was Eagle’s minimal essential medium (MEM). The mixture was then added to the Calu-3 cell layers and incubated for 60 min at 37oC, after which the cell layers were fixed with 4% paraformaldehyde for 15 min at 37oC. The cells were washed with phosphate buffered saline (PBS) and blocked in 1% bovine serum albumin (BSA) in PBS at 4oC overnight. They were then washed in PBS, incubated with 1 µg / mL of anti-His antibody, and then with an AlexaFlour 568 conjugated anti-mouse secondary antibody; incubations were for 60 min at 37oC. The coverslips were washed and mounted for viewing with a Nikon confocal microscope.

[0321] The results are shown in Figure 1. G22 was shown to be the most potent inhibitor of RBD binding to Calu-3 cells. Heparin and G24 also inhibited RBD binding to Calu-3 cells, but G17 did not demonstrate significant inhibition.EXAMPLE 15 – Ability of G4, G17, G19, G22 and G24 to inhibit SARS-CoV-2 viral infection of Vero E6 monkey kidney cells

[0322] Cell lines were obtained from the European Collection of Authenticated Cell Cultures (ECACC), UK Health Security Agency (UKHSA), Porton Down, UK. SARS- CoV-2 (hCoV-19 / Australia / VIC01 / 2020) (Victoria isolate) was provided by The Doherty Institute, Melbourne, Australia at P1 and passaged twice in Vero / hSLAM cells [ECACC 04091501]. Whole genome sequencing was performed, on the working stock at Passage 3, using both Nanopore and Illumina technologies and no significant changes in the viral sequence were observed. Virus titre was determined by a focus forming assay on Vero- E6 cells [ECACC 85020206]. Cell cultures were maintained at 37°C in minimal essential media (MEM) (Life Technologies, California, USA) supplemented with 10% foetal bovine serum (FBS) (Sigma, Dorset, UK) and 25 mM 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES; Life Technologies, California, USA), 2 mM L- Glutamine (Gibco, Thermo Fisher Scientific Inc., Waltham, MA, USA) and 1x Non- Essential Amino Acids Solution (Gibco, Thermo Fisher Scientific Inc., Waltham, MA, USA). In addition, Vero / hSLAM cultures were supplemented with 0.4 mg / mL of geneticin (Invitrogen, Thermo Fisher Scientific Inc., Waltham, MA, USA) to maintain stable integration of pCAG-hSLAM and expression of the human signalling lymphocytic activation molecule (hSLAM). Different variants of concern were cultured in a similar way to the Victoria isolate, from clinical samples at UKHSA, Porton Down.

[0323] Vero E6 Monkey kidney cells (EACC 85020206) were seeded into a 96- well plate. After 24 hours, the test compound [G4, G17, G19, G22, G24 (made in accordance with Examples 1-12) or unfractionated heparin] was serially diluted and each dilution was mixed with a fixed number of PFU (e.g. 70) of SARS-CoV-2 virus (hCoV- 19 / Australia / VIC01 / 2020) (50:50) and incubated for 1 hour at 37ºC, in a 96-well plate. The virus / compound mixture was added to the monolayer and virus was allowed to adsorb for 1 hour at 37ºC. After 1 hour the mixture was removed and the overlay media was added to each well, containing the diluted compound. Plates were incubated for 24 hours at 37ºC. The cells were fixed using 8% formalin for >8 hrs and then an immunostaining protocol using an anti-Spike protein antibody was performed on the fixed cells. Stained foci were counted using an ELISpot counter (Cellular Technology Limited (CTL)). The counted foci data were then imported into R-Bioconductor. A positive control, chloroquine biphosphate (50–0.02 µM), was run alongside the test compounds, on each assay plate.

[0324] The results are presented in Table 2 and Figures 2 (run 1) and 3 (run 2).TABLE 2: INHIBITION OF VIRAL INFECTION OF VERO E6 MONKEY KIDNEY CELLS. Run 1 Run 2 95% 95% e 6 9 2 7

[0325] The ability of G24 to inhibit different SARS-CoV-2 variants was assessed using the protocol described above. In brief, Vero E6 Monkey kidney cells (EACC 85020206) were seeded into a 96-well plate. After 24 hours, G24 (made in accordance with Example 6) was serially diluted and each dilution was mixed with a fixed number of PFU (e.g. 70) of SARS-CoV-2 virus [hCoV-19 / Australia / VIC01 / 2020 (Victoria, Wuhan-like isolate), Delta variant, Omicron variants or Beta variant] (50:50) and incubated for 1 hour at 37ºC, in a 96-well plate. The virus / compound mixture was added to the Vero E6 Monkey kidney cells monolayer and virus was allowed to adsorb to the cells for 1 hour at 37ºC. After 1 hour the mixture was removed and the overlay media (1% carboxymethylcellulose) was added to each well, containing the diluted compound. Plates were incubated for 20-26 hours depending on the variant at 37ºC. The cells were fixed using 8% formalin for >8 hrs and then an immunostaining protocol was performed on the fixed cells. For assays involving the Omicron variants the following was done. After formalin fixation the cells were washed and permeabilised with 0.2% (w / v) Triton X-100 / PBS at room temperature for 10 min, then washed with PBS, incubated with 0.3%hydrogen peroxide at room temperature for 20 mins and washed with PBS. Foci were stained with a rabbit anti-nucleocapsid antibody diluted in 0.2% (w / v) Triton X-100 / PBS for 1 h at room temperature, then washed and stained with a goat anti-rabbit immunoglobulin antibody coupled with horse radish peroxidase (HRP) diluted in the same buffer. Following washing, incubation with TrueBlue peroxidase substrate (SeraCare Life Sciences Inc., Milford, Massachusetts, USA) for 10 min at room temperature and washing completed the procedure. Stained foci were counted using an ELISpot counter (Cellular Technology Limited (CTL)). The counted foci data were then imported into R- Bioconductor. A positive control, chloroquine biphosphate (50–0.02 µM), was run alongside the test compound, on each assay plate. A mid-point probit analysis (written in R programming language for statistical computing and graphics) was used to determine the amount of compound (μg / mL) required to inhibit SARS-CoV-2 infectious viral foci by 50% (IC50) compared with the virus only control.

[0326] The results are presented in Table 3. TABLE 3: INHIBITION OF VIRAL INFECTION OF VERO E6 MONKEY KIDNEY CELLS WITH SARS- COV-2 VARIANTS BY G24. No. of biological IC50 (μg / mL) (± SARS-CoV-2 replicates IC50 (μg / mL) (± SD) of controlxis

[0327] These experiments were performed using DMSO treated human promyelocytic HL-60 cells. These cells were derived from a patient with acute promyelocytic leukemia. The cells were treated with DMSO (1.2%) for 4 days before being used in the experiments. The chemotaxis assays were performed in 96-well Costar chemotaxis plates consisting of a bottom chamber to which was added the human IL-8, with or without the addition of G19, G22 or G24 (made in accordance with Examples 6, 9 and 10; 50 μg / mL). Cells in RPMI and 1% v / v FCS were added to a top chamber and the plate was incubated at 37 ^C for 1 hour to allow cells to move from the top chamber into the bottom. The number of cells migrating into the bottom chamber was quantified bylabeling with AQUEOUS ONE (20 μL / well) for 1.75 hours before absorbance at 490 nm is read. IL-8 was used at a final concentration of 20 ng / mL. Mean and upper and lower limits are represented.

[0328] The results are presented in Figure 4, which shows the percentage inhibition in the presence of G19, G22 or G24. All three compounds inhibited IL-8 dependent chemotaxis, with G24 causing the greatest inhibition.

[0329] The disclosure of every patent, patent application, and publication cited herein is hereby incorporated herein by reference in its entirety.

[0330] The citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.

[0331] Throughout the specification the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features. Those of skill in the art will therefore appreciate that, in light of the instant disclosure, various modifications and changes can be made in the particular embodiments exemplified without departing from the scope of the present invention. All such modifications and changes are intended to be included within the scope of the appended claims.

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A compound of Formula I, II or III:wherein:L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L2, L5and L14are independently selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X1, X2, X3, X4, X5, X6, X7, X8, X9, X10and X11are independently selected from CH and N; and R1is selected from optionally substituted C2-C12 alkyl, optionally substituted C2-C12 alkenyl and optionally substituted C2-C12 alkynyl.

2. The compound according to claim 1, wherein X1-X11are CH.

3. The compound according to claim 1 or claim 2, wherein L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are optionally substituted C1-C3 alkylene.

4. The compound according to claim 3, wherein L1, L3, L4, L6, L7, L8, L9, L10, L11, L12, L13, L15, L16, L17, L18and L19are methylene.

5. The compound according to any one of claims 1-4, wherein L2is optionally substituted C2-C5 alkylene.

6. The compound according to claim 5, wherein L2is propylene.

7. The compound according to any one of claims 1-6, wherein L5is optionally substituted C3-C6 alkylene.

8. The compound according to claim 7, wherein L5is butylene.

9. The compound according to any one of claims 1-8, wherein L14is optionally substituted C2-C4 alkylene.

10. The compound according to claim 9, wherein L14is ethylene.

11. The compound according to any one of claims 1-10, wherein R1is optionally substituted C6-C10 alkyl.

12. The compound according to claim 11, wherein R1is octyl.

13. The compound according to any one of claims 1-12, wherein the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof:

14. The compound according to any one of claims 1-13, wherein the compound is in the form of a salt and the salt is the sodium salt.

15. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 and a pharmaceutically acceptable carrier or diluent.

16. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 for use in therapy.

17. A method of treating or inhibiting the development of a viral infection in a subject comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject:

18. The method according to claim 17, wherein the infection is caused by a virus expressing a viral fusion protein.

19. The method according to claim 17 or claim 18, wherein the infection is caused by an enveloped virus.

20. The method according to any one of claims 17-19, wherein the infection is caused by a virus that interacts with an ACE2 polypeptide-expressing cell.

21. The method according to any one of claims 17-20, wherein the viral infection is a coronavirus infection.

22. A method of inhibiting the interaction of a virus with an ACE2 polypeptide- expressing cell, comprising, consisting or consisting essentially of contacting the virus with a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof.

23. The method according to claim 22, wherein the interaction is one or both of binding of the virus to the cell and entry of the virus into the cell.

24. The method according to claim 22 or claim 23, wherein the cell is a lung cell (e.g. an alveolar cell), an enterocyte, an endothelial cell, an epithelial cell (e.g. a nasal or nasopharyngeal epithelial cell), a kidney cell (e.g. brush border of proximal tubular epithelial cells) or an arterial smooth muscle cell.

25. The method according to any one of claims 22-24, wherein the cell is a cell of the respiratory tract.

26. The method according to any one of claims 22-25, wherein the virus is a coronavirus.

27. A method of treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

28. A method of treating cytokine release syndrome (CRS) or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

29. A method of treating SARS in a subject, wherein the SARS is associated with a coronavirus infection, comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject.

30. The method according to any one of claims 21 and 26-29, wherein the coronavirus is a betacoronavirus.

31. The method according to claim 30, wherein the betacoronavirus is selected from SARS-CoV and SARS-CoV-2.

32. The method according to claim 31, wherein the betacoronavirus is SARS- CoV-2.

33. The method according to any one of claims 17-32, further comprising administering a second compound of Formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

34. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating or inhibiting the development of a viral infection in a subject.

35. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection.

36. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.

37. Use of a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof in the manufacture of a medicament for treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.

38. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating or inhibiting the development of a viral infection in a subject.

39. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating an acute inflammatory condition in a subject, wherein the condition is associated with a coronavirus infection.

40. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating CRS or a cytokine storm in a subject, wherein the CRS or cytokine storm is associated with a coronavirus infection.

41. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in treating SARS in a subject, wherein the SARS is associated with a coronavirus infection.

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