Use of alotaketal compounds and derivatives thereof as antiviral agents

Abstract

The present disclosure provides, for example, uses of compounds such as a compound of Formula (I) in the treatment of viral infections, for example, viral infections caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus (e.g., Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus, respiratory syncytial virus or combinations thereof), in a subject in need thereof.

Description

USE OF ALOTAKETAL COMPOUNDS AND DERIVATIVES THEREOF AS ANTIVIRAL AGENTSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of priority from co-pending U.S. provisional application no. 63 / 715,174 filed on November 1, 2024, the contents of which are incorporated herein by reference in their entirety.FIELD

[0002] The present disclosure relates, for example, to uses of Alotaketal compounds and derivatives thereof for use in the treatment of viral infections, for example, viral infections caused by one or more of a Kitrinoviricota virus and a Negarnaviricola virus (e.g., Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus, respiratory syncytial virus or combinations thereof), in a subject in need thereof.BACKGROUND

[0003] The twenty-first century has been marked by increased viral epidemics and pandemics, intensified by globalization and climate change, highlighting a challenge to public health with a lack and inequities of tools to advocate for health. Many pathogenic viruses can potentially emerge or re-emerge unexpectedly in human populations, representing an ongoing threat to global health. The problem of emerging and re-emerging viral infection is exacerbated by ongoing global climate changes, leading to shifts in the prevalence of zoonotic diseases and creating fertile grounds for vectors to increase and expand to new regions. In the 21st century, humankind witnessed several viral outbreaks, with a majority related to zoonotic or vector-home infections, such as influenza A virus (IAV; e.g., H1N1 2009), ebolavirus (EBOV; 2013-2016), arboviruses (ZIKV; 2015), and coronaviruses (SARS-CoV; 2003; and MERS-CoV; 2012).

[0004] IAV currently circulates in humans and is responsible for seasonal flu outbreaks as well as several pandemics including pandemic H1N1 in 1918, H2N2 in 1957, H3N2 in 1968, and H1N1 in 2009. Yearly, influenza viruses infect between 5% and 15% of the population with higher incidences (approximately 30%) in children. The highly pathogenic H5N1 influenza 2020 outbreak caused millions of cases of avian flu across the globe, most recently the vims has spread to mammals, including domestic cattle, creating fears about the risk for humans.

[0005] Zika virus is a mosquito-borne vims that currently does not have a fully approved vaccine or medicine to treat the infection. While many individuals infected with Zika virushave mild or no symptoms, a Zika virus infection during pregnancy can pose significant risks to the unborn baby, including microcephaly and other congenital abnormalities in the fetus.

[0006] Dengue virus is another viral infection that is transmitted to humans through the bite of an infected mosquito, and the incidence of dengue virus has experienced significant growth in recent decades, increasing from about 500,000 cases in 2000 to 6.5 million in 2023. Currently, there is no specific treatment for a dengue infection, and vaccines are limited and are targeted to specific populations.

[0007] Respiratory syncytial virus (RSV) is a common respiratory virus that spreads during seasonal outbreaks along with other respiratory viruses. However, children and the elderly can develop severe illness from RSV, including pediatric bronchiolitis and elderly pneumonia, respectively. Yearly, RSV contributes to 31% of pneumonia cases and 33 million cases of lower respiratory infections globally.

[0008] Current viral treatments include vaccines, mRNA vaccines, and monoclonal antibodies targeting the virus pathogen with diminishing efficacy due to viral mutations. For example, vaccines have significantly limited viral spread and have reduced hospitalizations. However, some viruses continue to evolve and escape vaccine-mediated immunity. It would be desirable for the global community to have equitable, accessible and effective new broadspectrum anti-viral drugs, to treat those such as children and families infected with viruses that produce respiratory diseases such as influenza, Dengue, Zika and / or RSV. It would also be desirable for the global community to have access to broad-spectrum anti-viral drugs that could address the so-called ‘tripledemic’ of influenza, RSV, and COVID- 19; or mosquito- borne virus coinfection of Dengue, Zika and Chikungunya virus.

[0009] Natural products (NPs) are a promising, but undervalued resource for new antivirals. Compounds derived from diverse sources can encompass structural diversity that falls outside the scope of chemical spaces found in synthetic chemical compounds, they have the potential to act via a mechanism distinct from those of conventional therapies. NPs have been highlighted for their antiviral potential against a variety of viruses, with potential novel inhibitors and activators of biological pathways, able to inhibit influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus (serotypes 1-4), Zika virus and RSV infections. It can be challenging to predict the antiviral potential of a particular NP. However, natural products are still considered a rich resource for novel antiviral drug development. Apart from plant-derived compounds, like Nigella sativa with inhibitory activity against the hepatitisC virus, several marine products (Wang 2014, Wang M 2016) have also been reported for their antiviral capacities against different viruses. Some natural products have been found through the inhibition of viral replication (Moghadamtousi 2015, Oliveira 2017). The antiviral activity can be performed based on their capability to inhibit viral entry, viral DNA and RNA synthesis, as well as viral reproduction, but they can also modulate cellular biological functions offering a broad-spectrum antiviral activity (Musarra-Pizzo 2021). They may, for example, have the advantages of a better toxicological profde, fewer side effects and / or a faster admission process in comparison to chemically engineering drugs. Some NPs have proved promising against coronaviruses, like SARS-CoV and MERS-CoV (Mani 2020, Ashhurst 2021).

[0010] Alotaketal C is a sesterterpenoid isolated from the marine sponge Phorbas sp. collected in Canada, it was shown to pose a stronger response than prostratin and activates proteins Kinase C (PKC), acting as provirus expression for latent HIV-1 (Wang 2016). Prostratin can activate latent virus reservoirs while preventing healthy cells from infection (Beans 2013). AkC has also been reported to potently inhibit the infection of human Calu-3 lung cells by SARS- CoV-2 Omicron BA.1 and BA.5 variants (Blagojevic et al., 2023). Analogs of AkC which are missing the C-l l substituents and have modified C-13 appendages (Scheme 1), have been reported to be about 2- to 7-fold more potent than AkC and to have equal or larger selectivity indices. PCT Publication No. 2023 / 173232 discloses Alotaketal compounds and derivatives thereof for use as antiviral agents in the treatment or prevention of coronavirus infection.Scheme 1: Chemical structures of AkC (left) and selected analogs (center and right).SUMMARY

[0011] The present disclosure includes a use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor 0Rfor Rband Rcjointly form =C R-'R1';Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, for treatment of a viral infection caused by one or more of a Kilrinoviricola virus and a Negarnaviricola virus, in a subject in need thereof.

[0012] The present disclosure also includes a use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3. locycloalkenyl or C3-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3-iocycloalkenyl or C3. locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor ORfor Rband Rcjointly form =C R-'R1';Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3. 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3. 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, C3-iocycloalkyl, C3-iocycloalkenyl or C3-iocycloalkynyl, wherein one ormore available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, in the preparation of a medicament for treatment of a viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricola virus, in a subject in need thereof.

[0013] In an embodiment, X is absent, and the compound of Formula (I) is a compound of Formula 1(a):1(a) 5 wherein Re2, R4, Ra, Rb, Rcand Rdare as described herein.

[0014] In an embodiment, Re2is unsubstituted Ci-ealkyl.

[0015] In another embodiment, Re2is methyl.

[0016] In an embodiment, X is O, and the compound of Formula (I) is a compound ofFormula 1(b):Kb) wherein X3, R4, Ra, Rb, Rcand Rdare as described herein.

[0017] In an embodiment, the compound of Formula 1(b) has the following stereochemistry:

[0018] In an embodiment, X3and X4are O.

[0019] In an embodiment, Rais H.

[0020] In an embodiment, Rband Rcare H.

[0021] In an embodiment, Rbis AcO and Rcis CH3.

[0022] In an embodiment, Rdis unsubstituted Cs-i2alkyl or Cs-i2alkenyl.

[0023] In another embodiment, Rdis -(CH2)nCHCH2, wherein n is an integer from 4 to 12.

[0024] In an embodiment, the compound of Formula (I) is selected from:

[0025] In an embodiment, the compound of Formula (I) has the structure:

[0026] In an embodiment, the compound of Formula (I) has the structure:

[0027] In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is for use in the form of a pharmaceutical composition comprising the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof and optionally a pharmaceutically acceptable excipient.

[0028] In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is in the form of the compound of Formula (I).

[0029] In an embodiment, the viral infection is caused by a filovirus, an orthomyxovirus, an arenavirus, a togavirus, a flavivirus, a pneumovirus or combinations thereof. In another embodiment, the viral infection is caused by Marburg vims, influenza vims, Lassa virus, chikungunya vims, dengue vims, Zika virus, respiratory syncytial virus or combinations thereof.

[0030] In an embodiment, the viral infection is caused by Marburg virus.

[0031] In an embodiment, the viral infection comprises infection with a combination of influenza virus and respiratory syncytial vims.

[0032] In an embodiment, the viral infection is caused by influenza virus.

[0033] In an embodiment, the influenza vims is an influenza A vims (IAV).

[0034] In an embodiment, the viral infection is caused by respiratory syncytial vims.

[0035] In an embodiment, the viral infection is caused by Lassa virus.

[0036] In an embodiment, the viral infection is caused by chikungunya virus.

[0037] In an embodiment, the viral infection is caused by dengue virus.

[0038] In an embodiment, the viral infection is caused by Zika virus.

[0039] In an embodiment, the subj ect is a human.

[0040] The present disclosure also includes a use of Alotaketal compounds and derivatives thereof having antiviral activity. For example, the present disclosure provides a use of a subsetof compounds represented by Formulas 1, 2 and 3, as antiviral agents in the treatment or prevention of influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus (serotypes 1-4), Zika virus, and / or respiratory syncytial virus (RSV) infections. Methods for using the compounds in the treatment or prophylaxis of influenza, Dengue, Zika, and / or RSV infection are also provided. In particular, influenza, Marburg, Lassa, Chikungunya, Dengue, Zika, and / or RSV infection may be selected from one or more of the following: H1N 1 influenza A virus (IAV / H1N1), an H5 avian influenza A virus, an H7 avian influenza A virus, an influenza B virus, Dengue virus (serotypes 1-4), Zika virus, a Marburg virus, a Lassa virus, a Chikungunya virus, and a respiratory syncytial virus infection (RSV). More specifically, the infection may be a human IAV / H1N1, Dengue virus, Zika and / or RSV infection.

[0041] Also provided herein are methods for a use of Alotaketal compounds and derivatives thereof that have antiviral activity. For example, the present disclosure provides a use of a subset of compounds represented by Formulas 1, 2 and 3, for use as antiviral agents in the treatment or prevention of an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus, and / or a respiratory syncytial virus (RSV) infection. Methods for using the compounds in the treatment or prophylaxis of an influenza, Dengue, Zika, and / or RSV infection are provided. In particular, the influenza, Marburg, Lassa, Chikungunya, Dengue, Zika and / or RSV infection may be selected from one or more of the following: H1N1 influenza A virus (IAV / H1N1) infection; H5 avian influenza A virus infection; H7 avian influenza A virus infection; influenza B virus infection; Marburg virus infection; Lassa virus infection; Chikungunya virus infection; Dengue virus infection; Zika virus infection; and respiratory syncytial virus (RSV) infection. More specifically, the influenza, Dengue, Zika, and / or RSV infection may be a human IAV / H1N1, Dengue (serotype 1-4), Zika, and / or RSV infection.

[0042] Other features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the disclosure, are given by way of illustration only and the scope of the claims should not be limited by these embodiments, but should rather be given the broadest interpretation consistent with the description as a whole.BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The embodiments of the disclosure will now be described in greater detail with reference to the attached drawings, in which:

[0044] FIGs. 1-6 show associated luciferase assay results of Alotaketal C (AkC) and analogues 22, 23, 17 and 19 entry inhibition of Ha-pseudo viruses. Cells were pre-treated for 1 h with 200 nM of inhibitors before 18 h infection with Ha-pseudovirus. Viral entry was quantified by luciferase assay. Data are normalized to quantification of luciferase with only pseudovirus. FIG. 1 is a plot showing results for IAV / H5Nl / Thailand / 2006, FIG. 2 is a plot showing results for IAV / H5N1 / Texas / 2O24, FIG. 3 is a plot showing results for Marburg virus, FIG. 4 is a plot showing results for Lassa virus, FIG. 5 is a plot showing results for Chikungunya virus, and FIG. 6 is a plot showing results for SARS-CoV-2 Omicron JN1.

[0045] FIG. 7 shows results of blocking infection of the RSV with AkC in human Calu-3 cells. Dose-response were curves generated for AkC in Calu-3 cells infected with RSV using dsRNA (circles) as infection markers (n = 3).

[0046] FIG. 8 shows results of blocking infection of the IAV / H1N1 with AkC in human Calu-3 cells. Dose-response curves were generated for AkC in Calu-3 cells infected with IAV / H1N1 / 2009 using dsRNA (squares) and hemagglutinin (HA) (circles) as infection markers (n=3).

[0047] FIGs. 9-14 show results of blocking infection of the IAV / H1N1 with selected AkC analogs and selected influenza antiviral treatments in human Calu-3 cells. Dose-response curves were generated for AkC analogs 22 (FIG. 9), 23 (FIG. 10) and 19 (FIG. 11) and selected influenza antiviral treatments Oseltamivir (FIG. 12), Baloxavir (FIG. 13), and EIDD- 1931 (FIG. 14) in Calu-3 cells infected with IAV / H1N1 using dsRNA (triangles) and hemagglutinin (HA) (circles) as infection markers (n = 2).

[0048] FIGs. 15-20 show results of blocking infection of the dengue virus serotype 2 (DENV2) with selected AkC analogs and selected protein kinase C (PKC) inhibitors in human Huh 7.5.1 cells. Dose-response curves were generated for AkC analogs 22 (FIG. 15), 23 (FIG. 16), 17 (FIG. 17) and 19 (FIG. 18) and selected PKC inhibitors Go6983 (a broad-spectrum PKC inhibitor; FIG. 19) and CRT0066854 (an atypical PKC inhibitor; FIG. 20) in human Huh 7.5. 1 cells infected with Dengue virus serotype 2 (DENV2) using dsRNA (triangles) and NS4B (circles) as infection markers. The graphs show a single experiment (n=2).

[0049] FIGs. 21-26 show results of blocking infection of the Zika virus (ZIKV) with selected AkC analogs and selected PKC inhibitors in human Huh 7.5.1 cells. Dose-response curves were generated for AkC analogs 22 (FIG. 21), 23 (FIG. 22), 17 (FIG. 23) and 19 (FIG. 24) and selected PKC inhibitors Go6983 (FIG. 25) and CRT0066854 (FIG. 26) in human Huh7.5.1 cells infected with Zika virus (ZIKV) using dsRNA (triangles) and NS4B (circles) as infection markers. The graphs show a single experiment (n=2).

[0050] FIG. 27 shows that compound AkC-19 reduced IAV H1N1 infection in air-liquid interface (ALI)-cultured primary human nasal epithelial cells (HNEpC), using NS1 as an infection marker for quantification and then normalized to DMSO-treated cells. The graph shows 3 independent experiments (n=3).

[0051] FIGs. 28-33 show results of blocking infection of IAV / H1N1 with selected AkC analogs in human Calu-3 cells. Dose-response curves were generated for AkC analogs 19 (FIG. 28), 24 (FIG. 29), 25 (FIG. 30), 26 (FIG. 31), 27 (FIG. 32) and 28 (FIG. 33) (n = 3) using hemagglutinin (HA) as infection markers (n = 3).

[0052] FIG. 34 shows the results of blocking infection of IAV / H5N1 with selected AkC analogs in human Calu-3 cells. Viral entry inhibition was quantified by luciferase assay. Doseresponse curves determined using nonlinear regression analysis were generated for AkC analogs 17 and 19.

[0053] FIG. 35 is a schematic illustrating the design of the Ha-H5N1 vector.

[0054] FIGs. 36-38 show characterization of AkC analog 26 enantiomers. FIG. 36 shows a high resolution mass spectrum (M + H)+, FIG. 37 shows a ID proton NMR spectrum (600 MHz - 0 to 8 ppm) and FIG. 38 shows a ID carbon NMR spectrum (150 MHz - 0 to 160 ppm) for the mixture of the enantiomers of AKC-26. The NMR spectra were recorded in benzene-de.DETAILED DESCRIPTIONI, Definitions

[0055] Unless otherwise indicated, the definitions and embodiments described in this and other sections are intended to be applicable to all embodiments and aspects of the disclosure herein described for which they would be understood to be suitable by a person skilled in the art. Any terms not directly defined herein shall be understood to have the meanings commonly associated with them as understood within the art of the invention.

[0056] As used herein, the words “comprising” (and any form thereof, such as “comprise” and “comprises”), “having” (and any form thereof, such as “have” and “has”), “including” (and any form thereof, such as “include” and “includes”) or “containing” (and any form thereof, such as “contain” and “contains”), are inclusive or open-ended and do not exclude additional, unrecited elements or process / method steps. As used herein, the word “consisting” and its derivatives areintended to be close-ended terms that specify the presence of the stated features, elements, components, groups, integers and / or steps, and also exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The term “consisting essentially of’, as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and / or steps as well as those that do not materially affect the basic and novel characteristic(s) of these features, elements, components, groups, integers and / or steps.

[0057] Terms of degree such as “substantially”, “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the term it modifies.

[0058] As used in this disclosure, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise.

[0059] The term “and / or” as used herein means that the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of’ or “one or more” of the listed items is present or used.

[0060] Whenever a range is given herein, for example, a temperature range, a time range, or a composition or concentration range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the disclosure. It will also be understood that any subranges or individual values in a range or subrange that are included in the description herein can be excluded from the aspects herein.

[0061] The term “halo” as used herein refers to a halogen atom and includes F, Cl, Br and I. In an embodiment of the present disclosure, halo is fluoro, chloro or bromo.

[0062] The term “alkylene” as used herein, whether it is used alone or as part of another group, means a straight or branched chain, bivalent form of an alkane, that is, a saturated carbon chain that links two other groups. In an embodiment, the alkylene is a Ci-ealkylene. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the numerical prefix “Cni-n2” For example, the term Ci-ealkylene means an alkylene group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0063] The term “alkenyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkenyl groups. The number of carbon atoms that are possible in the referenced alkenyl group are indicated by the numerical prefix“Cni-n2” For example, the term C2-ioalkenyl means an alkenyl group having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and at least one double bond, for example 1-3, 1-2, 2 or 1 double bond.

[0064] The term “alkynyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkynyl groups. The number of carbon atoms that are possible in the referenced alkynyl group are indicated by the numerical prefix “Cni-n2” For example, the term C2-ioalkynyl means an alkynyl group having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and at least one triple bond, for example 1-3, 1-2 or 1 triple bond.

[0065] The term “cycloalkyl” as used herein, whether it is used alone or as part of another group, means a mono- or bicyclic, saturated cycloalkyl group. The number of carbon atoms that are possible in the referenced cycloalkyl group are indicated by the numerical prefix “Cni-n2” For example, the term Cs-iocycloalkyl means a cycloalkyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.

[0066] The term “cycloalkenyl” as used herein, whether it is used alone or as part of another group, means a mono- or bicyclic, unsaturated cycloalkenyl group. The number of carbon atoms that are possible in the referenced cycloalkenyl group are indicated by the numerical prefix “Cni-n2” For example, the term Cs-iocycloalkenyl means a cycloalkenyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and at least one double bond, for example 1-3, 1-2 or 1 double bond.

[0067] The term “cycloalkynyl” as used herein, whether it is used alone or as part of another group, means a mono- or bicyclic, unsaturated cycloalkynyl group. The number of carbon atoms that are possible in the referenced cycloalkynyl group are indicated by the numerical prefix “Cni-n2” For example, the term Cs-iocycloalkynyl means a cycloalkynyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and at least one triple bond, for example 1-3, 1-2 or 1 triple bond.

[0068] When a cycloalkyl, cycloalkenyl or cycloalkynyl group contains more than one cyclic structure or rings, the cyclic structures may be fused, bridged, spiro connected or linked by a single bond. The term “fused” as used herein in reference to a first cyclic structure being “fused” with a second cyclic structure means the first cyclic structure and the second cyclic structure share at least two adjacent atoms therebetween. The term “bridged” as used herein in reference to a first cyclic structure being “bridged” with a second cyclic structure means the first cyclic structure and the second cyclic structure share at least two non-adjacent atomstherebetween. The term “spiro connected” in reference to a first cyclic structure being “spiro connected” with a second cyclic structure means the first cyclic structure and the second cyclic structure share one atom therebetween.

[0069] The term “aryl” as used herein, whether used alone or as part of another group, refers to groups that contain at least one aromatic ring. When an aryl group contains more than one aromatic ring the term “aryl” as used herein includes condensed aromatic systems. In an embodiment, the aryl group contains from 6, 9, 10 or 14 atoms, such as phenyl, naphthyl, indanyl or anthracenyl. The number of carbon atoms that are possible in the referenced aryl group are indicated by the numerical prefix “Cni-n2” For example, the term Ce-ioaryl means an aryl group having 6, 7, 8, 9 or 10 carbon atoms.

[0070] The term “heteroaryl” as used herein, whether used alone or as part of another group, refers to an aromatic, ring-containing group having one or more multivalent heteroatoms (for example, heteroatoms independently selected from N, O and S), as a part of the ring structure. In an embodiment of the present disclosure, the heteroaryl includes at least 5 and up to 20 atoms in the ring(s). Heteroaryl groups may contain more than one ring.

[0071] The term “available”, as used herein in reference to “available hydrogens”, “available carbon atoms”, and the like refers to atoms that would be known to a person skilled in the art to be capable of modification and / or replacement by another atom or substituent.

[0072] In an embodiment, one or more available one or more available hydrogens in an alkyl group is / are optionally replaced with fluorine. Such groups may optionally be referred to herein as a “haloalkyl” group. The term “haloalkyl” as used herein refers to an alkyl group wherein one or more, including all of the available hydrogen atoms are replaced by a halogen atom. The number of carbon atoms that are possible in the referenced haloalkyl group are indicated by the numerical prefix “Cni-n2” For example, the term Ci-ehaloalkyl means a haloalkyl group having 1, 2, 3, 4, 5 or 6 carbon atoms. In an embodiment, the halogen is a fluorine, in which case the haloalkyl is optionally referred to herein as a “fluoroalkyl” group. It is an embodiment that all of the hydrogen atoms are replaced by fluorine atoms.

[0073] The term “substituted” as used herein in reference to a group refers to such a group wherein one or more, including all of the available hydrogen atoms are replaced by a substituent.

[0074] The term “subject” as used herein includes all members of the animal kingdom including mammals. For example, as used herein, a “subject” may be a human, non-humanprimate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc. In an embodiment, the subject is a human. The subject may be suspected of having or at risk for having a viral infection, such as an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus, and / or a respiratory syncytial virus (RSV). In another embodiment, the infection may be an IAV / H1N1, Dengue, Zika, and / or RSV infection. Diagnostic methods for various viral infections, are known to those of ordinary skill in the art.II, Methods of Treatment. Uses. Compositions and Kits

[0075] The present disclosure includes a method of treating a viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, in a subject in need thereof, the method comprising administering a compound of Formula (I):wherein- represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Cnioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor ORfor Rband Rcjointly form =C RsRh;Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof.

[0076] The present disclosure also includes a use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor 0Rfor Rband Rcjointly form =C R-'R1';Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, for treatment of a viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricola virus, in a subject in need thereof.

[0077] The present disclosure also includes a use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3-locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor ORfor Rband Rcjointly form =C R-'R1';Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, in the preparation of a medicament for treatment of a viral infection caused by one or more of aKilrinoviricola virus and aNegarnaviricola virus, in a subject in need thereof.

[0078] The present disclosure also includes a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor ORfor Rband Rcjointly form =C R-'R1';Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, for use in the treatment of a viral infection caused by one or more of a Kitrinoviricota virus and aNegarnaviricota virus, in a subject in need thereof.

[0079] In an embodiment, the viral infection is a co-infection of two or more viruses.

[0080] In an embodiment, the viral infection is caused by a fdovirus, an orthomyxovirus, an arenavirus, a togavirus, a flavivirus, a pneumovirus or combinations thereof. In another embodiment, the viral infection is caused by Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus, respiratory syncytial virus or combinations thereof. In another embodiment, the viral infection is caused by a combination of Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus and respiratory syncytial virus. In another embodiment, the viral infection is caused by Marburgvirus. In another embodiment, the viral infection comprises infection with a combination of influenza virus and respiratory syncytial virus. In another embodiment, the viral infection is caused by a combination of influenza virus and respiratory syncytial virus. In another embodiment, the viral infection is caused by influenza virus. In a further embodiment, the influenza virus is an influenza A virus (IAV). In an embodiment, the influenza virus is an H1N1 influenza A virus (IAV / H1N1), an H5 avian influenza A virus, an H7 avian influenza A virus or an influenza B virus. In another embodiment, the viral infection is caused by respiratory syncytial virus. In another embodiment, the viral infection is caused by Lassa virus. In another embodiment, the viral infection is caused by chikungunya virus. In another embodiment, the viral infection is caused by dengue virus.

[0081] The present disclosure also includes a method of preventing, inhibiting, or reducing the viral activity of a Kitrinoviricota virus and / or a Negarnaviricota virus, on or in a cell or a subject which comprises administering to the cell or the subject an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, solvate and / or prodrug thereof as described herein. The present disclosure also includes a use of a compound of Formula (I) or a pharmaceutically acceptable salt, solvate and / or prodrug thereof as described herein for preventing, inhibiting, or reducing the viral activity of a Kitrinoviricota virus and / or a Negarnaviricota virus, on or in a cell or a subject. The present disclosure also includes a use of a compound of Formula (I) or a pharmaceutically acceptable salt, solvate and / or prodrug thereof as described herein in the preparation of a medicament for preventing, inhibiting, or reducing the viral activity of a Kitrinoviricota virus and / or a Negarnaviricota virus, on or in a cell or a subject. The present disclosure also includes a compound of Formula (I) or a pharmaceutically acceptable salt, solvate and / or prodrug thereof as described herein for use in preventing, inhibiting, or reducing the viral activity of a Kitrinoviricota virus and / or a Negarnaviricota virus, on or in a cell or a subject. In an embodiment, the cell is in a subject. In an embodiment, the cell is in vitro. In an embodiment, the virus is a coinfection of two or more viruses. In an embodiment, the virus is a fdovirus, an orthomyxovirus, an arenavirus, a togavirus, a flavivirus, a pneumovirus or combinations thereof. In another embodiment, the virus is Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus, respiratory syncytial virus or combinations thereof. In another embodiment, the virus is a combination of Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus and respiratory syncytial virus. In another embodiment, the virus is Marburg virus. In another embodiment, the virus comprisesa combination of influenza virus and respiratory syncytial virus. In another embodiment, the virus is a combination of influenza virus and respiratory syncytial virus. In another embodiment, the virus is influenza virus. In a further embodiment, the influenza virus is an influenza A virus (IAV). In an embodiment, the influenza virus is an H1N1 influenza A virus (IAV / H1N1), an H5 avian influenza A virus, an H7 avian influenza A virus or an influenza B virus. In another embodiment, the virus is respiratory syncytial virus. In another embodiment, the virus is Lassa virus. In another embodiment, the virus is chikungunya virus. In another embodiment, the virus is dengue virus.

[0082] The term “alkyl” as used herein, for example, in reference to a compound of Formula (I) or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, whether it is used alone or as part of another group, means straight or branched chain, saturated alkyl groups. The number of carbon atoms that are possible in the referenced alkyl group are optionally indicated by the numerical prefix “Cni-n2” For example, the term Ci-ealkyl means an alkyl group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0083] A person skilled in the art would readily appreciate in which embodiments of the compound of Formula (I) may represent a single bond and in which embodiments may represent a double bond. For example, the skilled person would readily understand that when X3is O, S, N-OH or N-NH-R®, the bond attaching the X3to the remainder of Formula (I) is a double bond whereas when X3is O-Re2, the bond attaching the X3to the remainder of Formula (I) is a single bond. Similarly, the skilled person would readily appreciate that the carbon attached to X3could participate in a maximum of one double bond. Accordingly, if the bond attaching the X3to the remainder of Formula (I) is a double bond, the other attached to the carbon attached to X3is a single bond.

[0084] In an embodiment, X is absent, and the compound of Formula (I) is a compound of Formula 1(a):'(a)5 wherein Re2, R4, Ra, Rb, Rcand Rdare as described for the compound of Formula (I).

[0085] In an embodiment, Re2is H or optionally substituted Ci-ioalkyl. In another embodiment, H is unsubstituted Ci-ealkyl. In a further embodiment, Re2is methyl.

[0086] In an embodiment, X is O, and the compound of Formula (I) is a compound ofFormula 1(b):1(b) 5 wherein X3, R4, Ra, Rb, Rcand Rdare as described for the compound for Formula (I).

[0087] In an embodiment, the compound of Formula 1(b) has the following stereochemistry:

[0088] In an embodiment, X3is O. In another embodiment, X4is O. In a further embodiment, X3and X4are O. In another embodiment, RaX4is OH.

[0089] In an embodiment, Rais H or Ci-4alkyl. In another embodiment, Rais H.

[0090] In an embodiment, Rband Rcare each independently H, Rfor ORf. In another embodiment, Rband Rcare H. In a further embodiment, Rbis AcO and Rcis CH3.

[0091] In an embodiment, the substituents are independently selected from OR, =0, NH2, SH and halo, wherein R is selected from H, C(=O)CH3, C(=O)CH2CH(CH3)CH3 and Ci-ealkyl. In an embodiment, the substituents are independently selected from OR, =0, NH2, SH, F, Cl and Br, wherein R is selected from H, C(=O)CH3, C(=O)CH2CH(CH3)CH3 and CH3. In an embodiment, the substituents are independently selected from OH, F, Cl and Br. In an embodiment, the substitution is with OR, wherein R is selected from H, C(=O)CH3, C(=O)CH2CH(CH3)CH3 and CH3. In an embodiment, the substitution is with OR, wherein R is selected from C(=O)CH3, C(=O)CH2CH(CH3)CH3 and CH3. In an embodiment, the substitution is with OR, wherein R is C(=O)CH3. In an embodiment, the substitution is with OR, wherein R is C(=O)CH2CH(CH3)CH3. In an embodiment, the substitution is with OH. In an embodiment, Rdis unsubstituted Ci-2oalkyl or C2-2oalkenyl. In another embodiment, Rdis unsubstituted Cs- alkyl or Cs- alkenyl. In another embodiment, Rdis a linear Ci- 2oalkyl, a linear C2-2oalkenyl or a branched C4-2oalkenyl. In an embodiment, Rdis - (CH2)nCHCH2, wherein n is an integer from 4 to 12. In an embodiment, n is 8.

[0092] In an embodiment wherein one or more available carbon atoms is / are replaced with a heteroatom, the heteroatoms are selected from NR', O, S and combinations thereof, wherein each R' is independently H, alkyl or alkylene-aryl. In another embodiment, the heteroatoms are selected from NR', S and combinations thereof, wherein each R' is independently H, alkyl or alkylene-aryl. In another embodiment, the heteroatoms are selected from NR', S and combinations thereof, wherein each R' is independently H or alkyl. In a further embodiment, the alkyl is Ci-ealkyl.

[0093] In an embodiment, the compound of Formula (I) is selected from:

[0094] In an embodiment, the compound of Formula (I) has the structure:

[0095] In an embodiment, the compound of Formula (I) has the structure:

[0096] In an embodiment, the compound of Formula (I) has the structure:

[0097] In an embodiment, the compound of Formula (I) has the structure:

[0098] In an embodiment, the compound of Formula (I) has the structure:

[0099] In an embodiment, the compound of Formula (I), or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is in the form of the compound.

[0100] In an embodiment, the compound of Formula (I), or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is in the form of the pharmaceutically acceptable salt of the compound, solvate and / or prodrug thereof. In an embodiment, the compound of Formula (I), or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is in the form of the pharmaceutically acceptable salt of the compound. The term “pharmaceutically acceptable salt” as used herein, for example, in reference to the pharmaceutically acceptable salt of the compound of Formula (I) or the solvate and / or prodrug thereof means an acid addition salt or a base addition salt that is compatible with the treatment of subjects. An “acid addition salt that is compatible with the treatment of subjects” is any non-toxic inorganic or organic salt of any basic compound. Basic compounds that form an acid addition salt include, for example, compounds comprising an amine group susceptible to protonation. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulfuric and phosphoric acids, as well as metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Illustrative organic acids that may form suitable salts include mono-, di-, and tricarboxylic acids such as glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, benzoic, phenylacetic, cinnamic and salicylic acids, as well as sulfonic acids such as p-toluene sulfonic and methanesulfonic acids. Such salts may exist in a hydrated, solvated or substantially anhydrous form. The selection of a suitable salt can be made by a person skilled in the art. The formation of a desired acid addition salt is, for example, achieved using standard techniques. For example, in an embodiment of the present disclosure, the neutral compound is treated with the desired acid in a suitable solvent and the salt which is thereby formed then isolated by filtration, extraction and / or any other suitable method. A “base addition salt that is compatible with the treatment of subjects” is any non-toxic inorganic or organic salt of any acidic compound. Acidic compounds that form a base addition salt include, for example,compounds comprising a thiol group. Inorganic bases that may form suitable salts include, without limitation, lithium, sodium, potassium, calcium, magnesium or barium hydroxide. Organic bases that may form suitable salts include, without limitation, aliphatic, alicyclic or aromatic organic amines such as methylamine, trimethylamine and picoline or ammonia. Such salts may exist in a hydrated, solvated or substantially anhydrous form. The selection of a suitable salt can be made by a person skilled in the art. The formation of a desired base addition salt is, for example, achieved using standard techniques. For example, in an embodiment of the present disclosure, the neutral compound is treated with the desired base in a suitable solvent and the salt which is thereby formed then isolated by filtration, extraction and / or any other suitable method.

[0101] The term “prodrug” as used herein, for example, in reference to the compound of Formula (I) refers to a derivative of the compound of Formula (I) that reacts under biological conditions to provide the compound of Formula (I).

[0102] In an embodiment, the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for the compounds of Formula 1, 2 and / or 3. For example, X3in the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for X1; X4in the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for X2, Rain the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for R1; Rbin the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for R2, Rcin the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for R3and / or Rdin the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof may be varied as described herein for R4.

[0103] In an embodiment, the subject is a human.

[0104] The terms “to treat”, “treating” and “treatment” and the like as used herein and as is well understood in the art, means an approach for obtaining beneficial or desired results, including clinical results. For example, in the context of treating a viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, beneficial or desired clinical results include, but are not limited to alleviation or amelioration of one or moresymptoms of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, diminishment of the extent of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, stabilized (i.e., not worsening) of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, delay or slowing of the progression of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, amelioration or palliation of the disease state of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, diminishment of the reoccurrence of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, and / or remission (whether partial or total) of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, whether detectable or undetectable. In some embodiments, “to treat”, “treating” and “treatment” and the like as used herein also include prophylactic treatment of the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus.

[0105] The compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is, for example, administered to the subject or used in an “effective amount”. As used herein, for example, in reference to the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof, the term “effective amount” and the like means an amount effective, at dosages and for periods of time necessary to achieve a desired result. For example, in the context of treating a viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus, an effective amount of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof administered or used is an amount that, for example, reduces the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus compared to the viral infection caused by one or more of a Kitrinoviricota virus and a Negarnaviricota virus without administration or use of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof. Effective amounts may vary according to factors such as the disease state, age, sex, weight and / or species of the subject. The amount of a given compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof that will correspond to such an amount will vary depending upon various factors, such as the given compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof, the pharmaceutical formulation, the route of administration or use, the type of viral infection caused by one or more of a Kitrinoviricotavirus and aNegarnaviricota virus being treated, the identity of the subject being treated, and the like, but can nevertheless be routinely determined by one skilled in the art.

[0106] The compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof can be administered to a subject or used in a variety of forms depending on the selected route of administration or use, as will be understood by those skilled in the art. In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is for use in the form of a pharmaceutical composition comprising the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof and optionally a pharmaceutically acceptable excipient. In an embodiment, the pharmaceutical composition comprises the pharmaceutically acceptable excipient.

[0107] In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered to the subject, or used, by oral (including buccal) or parenteral (including intravenous, intraperitoneal, subcutaneous, intramuscular, transepithelial, nasal, intrapulmonary, intrathecal, rectal, topical, patch, pump and transdermal) administration or use and the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof formulated accordingly. For example, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used in an injection, in a spray, in a tablet / caplet, in a powder, topically, in a gel, in drops, by a patch, by an implant, by a slow release pump or by any other suitable method of administration or use, the selection of which can be made by a person skilled in the art.

[0108] In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is orally administered or used, for example, with an inert diluent or with an assimilable edible carrier, or enclosed in hard- or soft-shell gelatin capsules, or compressed into tablets, or incorporated directly with the food of the diet. In an embodiment, for oral therapeutic administration or use, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is incorporated with excipient and administered or used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Oral dosage forms also include modified release, for example immediate release and timed-release, formulations. Examples of modified-release formulations include, for example, sustained-release (SR), extended- release (ER, XR, or XL), time-release or timed-release, controlled-release (CR), or continuous-release (CR or Contin), employed, for example, in the form of a coated tablet, anosmotic delivery device, a coated capsule, a microencapsulated microsphere, an agglomerated particle, e.g., as molecular sieving type particles, or, a fine hollow permeable fiber bundle, or chopped hollow permeable fibers, agglomerated or held in a fibrous packet. Timed-release compositions can be formulated, e.g. liposomes or those wherein the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is protected with differentially degradable coatings, such as by microencapsulation, multiple coatings, etc.

[0109] In another embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used parenterally. Solutions of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof are, for example, prepared in water optionally mixed with a surfactant such as hydroxypropylcellulose. In a further example, dispersions are prepared in glycerol, liquid polyethylene glycols, dimethyl sulfoxide (DMSO) or mixtures thereof with or without alcohol, or in oils. Pharmaceutical forms suitable for injectable administration or use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. A person skilled in the art would know how to select and to prepare suitable formulations.

[0110] Treatment methods or uses comprise administering to a subject or use of an effective amount of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof, optionally consisting of a single administration or use, or alternatively comprising a series of administrations or uses. For example, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used at least once a week. However, in another embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered to the subject or used from one time per three weeks, or one time per week to once daily for a given treatment or use. In another embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used 2, 3, 4, 5 or 6 times daily. The length of the treatment period or use depends on a variety of factors, such as the severity and / or type of the viral infection caused by one or more of a Kitrinoviricota vims and a Negarnaviricota virus, the age of the subject, the concentration of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof in a formulation, the activity of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof and / or a combination thereof. It will also beappreciated that the effective amount of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof used for the treatment or use may increase or decrease over the course of a particular treatment regime or use. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration or use is required. For example, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used in an amount and for a duration sufficient to treat the subject.

[0111] The compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof may be administered or used alone or in combination with other therapeutic agents useful for treating a viral infection caused by one or more of aKitrinoviricota virus and a Negarnaviricota virus. When administered or used in combination with other known therapeutic agents, it is an embodiment that the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used contemporaneously with those therapeutic agents. As used herein the term “contemporaneous” in reference to administration of two substances to a subject or use means providing each of the two substances so that they are both biologically active in the individual at the same time. The exact details of the administration or use will depend on the pharmacokinetics of the two substances in the presence of each other, and can include administering or using the two substances within a few hours of each other, or even administering or using one substance within 24 hours of administration or use of the other, if the pharmacokinetics are suitable. Design of suitable dosing regimens is routine for one skilled in the art. In particular embodiments, two substances will be administered or used substantially simultaneously, i.e., within minutes of each other, or in a single composition that contains both substances. It is a further embodiment that a combination of the two substances is administered to a subject or used in a non-contemporaneous fashion.

[0112] The dosage of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof can vary depending on many factors such as the pharmacodynamic properties of the compound, the mode of administration or use, the age, health and weight of the subject, the nature and extent of the symptoms of the viral infection caused by one or more of a Kitrinoviricota vims and a Negarnaviricota vims, the frequency of the treatment or use and the type of concurrent treatment or use, if any, and the clearance rate of the compound in the subject. One of skill in the art can determine the appropriate dosagebased on the above factors. In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used initially in a suitable dosage that is optionally adjusted as required, depending on the clinical response. As a representative example, oral dosages of the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof will range from less than 1 mg per day to 1000 mg per day for a human adult or an animal. In an embodiment of the present disclosure, the pharmaceutical compositions are formulated for oral administration or use and the compounds of Formula (I) or the pharmaceutically acceptable salts, solvates and / or prodrugs thereof are, for example in the form of tablets containing 0.001, 0.01, 0.1, 0.25, 0.5, 0.75, 1.0, 5.0, 10.0, 20.0, 25.0, 30.0, 40.0, 50.0, 60.0, 70.0, 75.0, 80.0, 90.0, 100.0, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 mg of active ingredient per tablet. In an embodiment, the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is administered or used in a single daily dose or the total daily dose may be divided into two, three or four daily doses.III. Additional Embodiments

[0113] The present disclosure also includes a use of a subset of compounds represented by Formulas 1, 2 and 3 described herein as antiviral agents in the treatment or prevention of influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV infection. For example, it is shown herein that compounds having R4chiralityor the opposite chirality. Methods for using the compounds in the treatment or prophylaxis of an influenza, Marburg, Lassa, Chikungunya, Dengue, Zika and / or RSV infection are provided. In particular, the influenza, Marburg, Lassa, Chikungunya, Dengue, Zika, and / or RSV infection may be selected from one or more of the following: H1N1 influenza A virus (IAV / H1N1), an H5 avian influenza A virus an H7 avian influenza A virus, an influenza B virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus, and a respiratory syncytial virus infection, infection. More specifically, the infection may be ahumanlAV / HINl, Dengue, Zika, and / or RS V infection. In an embodiment, there is provided a method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus, and / or a respiratory syncytial virus (RSV) infection using a compound, the compound may have the structure of Formula 1:Formula iorpharmaceutical acceptable salt or prodrug thereof, wherein: X1may be selected from: O; S; N-OH; and N-NH-R5; X2may be selected from: O; and S; R1may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S; R2and R3may be independently selected from: H; R; OR; or R2 and R3 jointly form =CR6R7; R4may be selected from: a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with O, OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S; R5may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S; R6may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S; R7may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S; and R may be selected from: C(=0)CH3; C(=O)CH2CH(CH3)CH3; H; and CH3. In a further embodiment, there is a method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus and / or a respiratory syncytial virus (RSV) infection using a compound, the compound having the structure of Formula 3:Formula 3; wherein: R2is selected from: H; CH3; OC(=O)CH3; andOC(=O)CH2CH(CH3)CH3; R3is selected from: H; CH3; OC(=O)CH3; and OC(=O)CH2CH(CH3)CH3; alternatively, R2and R3jointly form =CH2; and R4is a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group where individual carbon atoms may be substituted with OH, =0, NH, SH, F, Cl, Br, or be replaced by N, or S. In a further embodiment, there is provided a method of treating an influenza and / or RSV infection in a subject in need thereof, the method including administration of a compound to the subject, wherein the compound is a compound described herein, or pharmaceutical acceptable salt or prodrug thereof. In a further embodiment, there is provided a use of a pharmaceutical composition, the pharmaceutical composition including a compound described herein, or pharmaceutical acceptable salt or prodrug thereof, for treatment of an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV infection. In a further embodiment, there is provided a use of a pharmaceutical composition, the pharmaceutical composition including (a) a compound of Formula 3 as described herein or pharmaceutical acceptable salt or prodrug thereof, and (b) a pharmaceutically acceptable carrier. In a further embodiment, there is provided a use of a compound, or pharmaceutical acceptable salt or prodrug thereof, or a pharmaceutical composition as described herein, for treating an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV infection. In a further embodiment, there is provided a use of a compound, or pharmaceutical acceptable salt or prodrug thereof, or a pharmaceutical composition as described herein, in the manufacture of a medicament for treating an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV infection. Alternatively, the method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, Dengue virus, Zika virus, and / or a respiratory syncytial virus (RSV) infection using a compound, wherein the compound may have thestructureAlternatively, R4may be a saturated, unsaturated, linear or branched Cs to C12 alkyl group. Alternatively, R4may be selected from:may be selected from: O; S; N-OH; and N-NH-R5. Alternatively, X1may be selected from: O; S; and N-OH. Alternatively, X1may be selected from: O; and S. Alternatively, X2may be selected from: O; and S. Alternatively, X2may be O. Alternatively, X2may be S. Alternatively, R1may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R1may be H. Alternatively, R1may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R1may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br. Alternatively, R1may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms or may be optionally replaced by N, or S. Alternatively, R2and R3may be independently selected from: H; R; OR; or R2 and R3 may jointly form =CR6R7. Alternatively, R2and R3may be independently selected from: H; R; OR. Alternatively, R2 and R3 may jointly form =CR6R7. Alternatively, R2and R3may be independently selected from: H; or R. Alternatively, R2and R3may be: H; or R. Alternatively, R2and R3may be H. Alternatively, R2and R3may be R. Alternatively, R2may be selected from:H; 0C(=0)CH3; and OC(=O)CH2CH(CH3)CH3; and R3 may be selected from: H; and CH3. Alternatively, R2may be H and R3 may be H. Alternatively, R4may be selected from: a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with O, OH, =0, NH, SH, F, Cl, and Br. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with O, OH, NH, F, Cl, and Br. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, =0, NH, SH, F, Cl, and Br. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with OH. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group. Alternatively, R4may be a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms are unsubstituted. Alternatively, R5may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R5may be H. Alternatively, R5may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R5may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R6may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R6may be H. Alternatively, R6may be a one to ten carbonsaturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R6may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R7may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or may be optionally replaced by N, or S. Alternatively, R7may be H. Alternatively, R7may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R7may be selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms may be optionally substituted with OH, OR, =0, NH, SH, F, Cl, and Br. Alternatively, R may be selected from: C(=0)CH3; C(=O)CH2CH(CH3)CH3; H; and CH3. Alternatively, R may be selected from: H; and CH3. Alternatively, R may be selected from: C(=0)CH3; H; and CH3. Alternatively, R may be selected from: C(=O)CH2CH(CH3)CH3; H; and CH3. Alternatively, R may be selected from:C(=0)CH3; and C(=O)CH2CH(CH3)CH3. Alternatively, R may be selected from: C(=0)CH3; C(=O)CH2CH(CH3)CH3; and CH3. Alternatively, R may be selected from: C(=0)CH3; C(=O)CH2CH(CH3)CH3; and H. Alternatively, R may be selected from: C(=0)CH3; and CH3. Alternatively, R may be selected from: C(=O)CH2CH(CH3)CH3; and CH3. Alternatively, R may be C(=0)CH3. Alternatively, R may be C(=O)CH2CH(CH3)CH3. Alternatively, R may be H. Alternatively, R may be CH3. Alternatively, R2and R3may be independently selected from: H; 0C(=0)CH3; OC(=O)CH2CH(CH3)CH3; and OH; or jointly are =CH2. Alternatively, X1may be selected from: O; and S; and X2is O. Alternatively, R1may be H. Alternatively, the method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, aDengue virus, a Zika virus, and / or a respiratory syncytial virus (RSV) infection is using a compound, wherein the compound may have the structure of FormulaFormula 2; wherein: R1may be selected from: H; and CH3C(0); R2may be 0C(=0)CH3; andRs is CH3; or R2and R3may jointly form =CH2; R4may be selected from: a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group where individual carbon atoms may be substituted with O, OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; and R may be selected from: C(=0)CH3; C(=O)CH2CH(CH3)CH3; H; andCH3. Alternatively, the compound may have the structure. Alternatively,R4may be a saturated, unsaturated, linear or branched Cs to C12 alkyl group. Alternatively, R4Alternatively, R4may be selected from:Alternatively, R4may be selected from:and R3may be independently selected from: H; OC(=O)CH3; OC(=O)CH2CH(CH3)CH3; andOH; or jointly are =CH2. Alternatively, X1may be selected from: O; and S; and X2is O. Alternatively, R1may be H. The compound may be selected from one or more of the following:The compound may be selected from one or more of the following:Alternatively, the compound may be selected from:Marburg, Lassa, Chikungunya, Dengue, Zika, and / or RSV infection may be selected from one or more of the following: H1N1 influenza A virus (IAV / H1N1), anH5 avian influenza A virus, an H7 avian influenza A virus, an influenza B virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and RSV infection. Influenza, Dengue, Zika, and / or RSV infection may be human IAV / H1N1, Dengue virus (serotypes 1-4), Zika, and / or RSV infection.

[0114] In a further aspect, there is provided a method of preventing, inhibiting, or reducing the viral activity of an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus, and / or RSV, such as IAV / H1N1, Dengue virus (serotypes 1- 4), Zika, and / or RSV, on or in a cell or a subject which comprises administering to the cell or the subject an effective amount of a compound having the structural formula depicted inFormula, wherein: Xi may be either O, S, N-OH, N-NH-R5; X2 may be either O or S; Ri is H, or a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms may be substituted with OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; R2 and R3 are independently H, R, OR, or R2 and R3 jointly form =CR6R7; R4 is a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group where individual carbon atoms may be substituted with O, OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; R5 may be a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms may be substituted with OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; Re may be H, a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms may be substituted with OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; R7 may be H, or a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms may be substituted with OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S.

[0115] Another aspect is a method of preventing, inhibiting, or reducing the viral activity of an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV, such as IAV / H1N1, Dengue virus (serotypes 1-4), Zika virus and / or RSV, on or in a cell or a subj ect which comprises administering to the cell or the subj ect an effective amount of a compound having the structural formula depicted in Formulawherein: Ri may be either H or CH3C(O), wherein either R2 is -OC(O)CH3 and R3 is CH3; or,R2 and R3 jointly form =CH2; R4 is a one to twenty carbon saturated, unsaturated, or aromatic,linear, branched, or cyclic alkyl group where individual carbon atoms may be substituted with O, OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S.

[0116] In yet another aspect, within the compounds of Formula 1 or Formula 2 the R4 moieties may be a linear Cs to C12 alkyl chain, or one of the following:

[0117] In another aspect, a method of preventing, inhibiting, or reducing the viral activity of an influenza virus, Marburg virus, Lassa virus, Chikungunya virus, Dengue virus, Zika virus and / or RSV, such as IAV / H1N1, Dengue virus (serotypes 1-4), Zika virus, and / or RSV, on or in a cell or a subject is provided which comprises administering to the cell or the subject an effective amount of a compound selected from the following group:

[0118] In one aspect, the virus is influenza virus IAV / H1N1, Dengue virus (serotypes 1- 4), Zika virus, and / or RSV.

[0119] In a further aspect described herein, a method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus, and / or a respiratory syncytial virus (RSV) infection using one or more compounds is provided, wherein the one or more compounds are selected from:

[0120] Embodiment 1. A method of treating an influenza virus, a Marburg virus, a Lassa virus, a Chikungunya virus, a Dengue virus, a Zika virus and / or a respiratory syncytial virus (RSV) infection in a subject in need thereof is provided, the method comprising administration of a compound to the subject, wherein the compound has the structure of Formula 1 :or pharmaceutical acceptable salt or prodrug thereof, wherein: X1is selected from: O; S; N- OH; and N-NH-R5; X2is selected from: O; and S; R1is selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms are optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or are optionally replaced by N, or S; R2and R3are independently selected from: H; R; OR; or R2 and R3 jointlyform =CR6R7; R4is selected from: a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group, where individual carbon atoms are optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or are optionally replaced by N, or S; R5is selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group, where individual carbon atoms are optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or are optionally replaced by N, or S; R6is selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic, alkyl group where individual carbon atoms are optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or are optionally replaced by N, or S; R7is selected from: H; and a one to ten carbon saturated, or unsaturated, linear, branched, or cyclic alkyl group where individual carbon atoms are optionally substituted with OH, OR, =0, NH, SH, F, Cl, Br, or are optionally replaced by N, or S; and R is selected from: C(=O)CH3; C(=O)CH2CH(CH3)CH3; H; and CH3.

[0121] Embodiment 2. The method of Embodiment 1, wherein the structure of Formula 1 is

[0122] Embodiment 3. The method of Embodiment 1 or 2, wherein R4is a saturated, unsaturated, linear or branched Cs to C12 alkyl group.

[0123] Embodiment 4. The method of Embodiment 1 or 2, wherein R4is selected from:

[0124] Embodiment 5. The method of Embodiment 1, wherein R2and R3are independently selected from: H; OC(=O)CH3; OC(=O)CH2CH(CH3)CH3; and OH; or jointly are =CH2.

[0125] Embodiment 6. The method of Embodiment 1, wherein X1is selected from: O; and S; and X2is O. Embodiment 7. The method of Embodiment 1, wherein R1is H.

[0126] Embodiment 8. The method of Embodiment 1 wherein the compound has the structure of Formula 2:wherein: R1is selected from: H; and CH3C O); R2is OC(=O)CH3; and R3 is CH3; or R2and R3jointly form =CH2; R4is selected from: a one to twenty carbon saturated, unsaturated, or aromatic, linear, branched, or cyclic alkyl group where individual carbon atoms may be substituted with OH, OR, =0, NH, SH, F, Cl, Br, or be replaced by N, or S; and R is selected from: C(=O)CH3; C(=O)CH2CH(CH3)CH3; H; and CH3.

[0127] Embodiment 9. The method of Embodiment 8, wherein the structure of Formula 2 is

[0128] Embodiment 10. The method of Embodiment 8 or 9, wherein R4is a saturated, unsaturated, linear or branched Cs to C12 alkyl group; or wherein R4is selected from:

[0129] Embodiment 11. The method of Embodiment 8, wherein R2and R3are independently selected from: H; OC(=O)CH3; OC(=O)CH2CH(CH3)CH3; and OH; or jointly are =CH2.

[0130] Embodiment 12. The method of Embodiment 8, wherein X1is selected from: O; and S; and X2is O. Embodiment 13. The method of Embodiment 8, wherein R1is H.

[0131] Embodiment 14. The method of Embodiment 1, wherein the compound is selectedr wherein the compound is selected from one or more of the following:

[0132] Embodiment 15. The method of Embodiment 1, wherein the influenza, Marburg, Lassa, Chikungunya, Dengue, Zika, and / or RSV infection is selected from one or more of the following: H1N1 influenza A virus (IAV / H1N1); H5 avian influenza A virus; H7 avian influenza A virus; influenza B vims; Marburg vims; Lassa virus; Chikungunya vims; Dengue virus; Zika virus; and respiratory syncytial vims (RSV) infection; or wherein the influenza, Dengue, Zika and / or RSV infection is ahuman lAV / HINl, Dengue (serotypes 1-4), Zika, and / or RSV infection.

[0133] Embodiment 16. The method of Embodiment 1, wherein the compound has the structure of Formula 3:wherein: R2is selected from: H; CH3; OC(=O)CH3; and OC(=O)CH2CH(CH3)CH3; R3 is selected from: H; CH3; OC(=O)CH3; and OC(=O)CH2CH(CH3)CH3; alternatively, R2and R3j ointly form =CH2; and R4is a one to twenty carbon saturated, unsaturated, or aromatic, linear,branched, or cyclic alkyl group where individual carbon atoms may be substituted with OH, =0, NH, SH, F, Cl, Br, or be replaced by N, or S.

[0134] Embodiment 17. The method of Embodiment 16, wherein R4is a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group; or wherein R4is a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with OH, =0, NH, SH, F, Cl, and Br; or wherein R4is a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with OH, NH, F, Cl, and Br; or wherein R4is a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms may be substituted with OH; or wherein R4is a one to twenty carbon saturated, unsaturated, linear, or branched alkyl group, where the individual carbon atoms are unsubstituted.

[0135] Embodiment 18. The method of Embodiment 16, wherein R2is selected from: H;OC(=O)CH3; and OC(=O)CH2CH(CH3)CH3; and R3 is selected from: H; and CH3.

[0136] Embodiment 19. The method of Embodiment 16, wherein R2is H and R3 is H.

[0137] Embodiment 20. The method of Embodiment 1 , wherein the compound is selected

[0138] Compounds, as described herein, may be in the free form or in the form of a salt thereof. In some embodiments, compounds, as described herein, may be in the form of apharmaceutically acceptable salts, which are known in the art. Pharmaceutically acceptable salt, as used herein, include, for example, salts that have the desired pharmacological activity of the parent compound (salts which retain the biological effectiveness and / or properties of the parent compound and which are not biologically and / or otherwise undesirable). Compounds, as described herein, having one or more functional groups capable of forming a salt, may be, for example, formed as a pharmaceutically acceptable salt. Compounds containing one or more basic functional groups may be capable of forming a pharmaceutically acceptable salt with, for example, a pharmaceutically acceptable organic or inorganic acid. Pharmaceutically acceptable salts may be derived from, for example, and without limitation, acetic acid, adipic acid, alginic acid, aspartic acid, ascorbic acid, benzoic acid, benzenesulfonic acid, butyric acid, cinnamic acid, citric acid, camphoric acid, camphorsulfonic acid, cyclopentanepropionic acid, diethylacetic acid, digluconic acid, dodecylsulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, glucoheptanoic acid, gluconic acid, glycerophosphoric acid, glycolic acid, hemisulfonic acid, heptanoic acid, hexanoic acid, hydrochloric acid, hydrobromic acid, hydriodic acid, 2-hydroxyethanesulfonic acid, isonicotinic acid, lactic acid, malic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, 2-napthalenesulfonic acid, naphthalenedisulphonic acid, p-toluenesulfonic acid, nicotinic acid, nitric acid, oxalic acid, pamoic acid, pectinic acid, 3-phenylpropionic acid, phosphoric acid, picric acid, pimelic acid, pivalic acid, propionic acid, pyruvic acid, salicylic acid, succinic acid, sulfuric acid, sulfamic acid, tartaric acid, thiocyanic acid or undecanoic acid. Compounds containing one or more acidic functional groups may be capable of forming pharmaceutically acceptable salts with a pharmaceutically acceptable base, for example, and without limitation, inorganic bases based on alkaline metals or alkaline earth metals or organic bases such as primary amine compounds, secondary amine compounds, tertiary amine compounds, quaternary amine compounds, substituted amines, naturally occurring substituted amines, cyclic amines or basic ion-exchange resins. Pharmaceutically acceptable salts may be derived from, for example, and without limitation, a hydroxide, carbonate, or bicarbonate of a pharmaceutically acceptable metal cation such as ammonium, sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese or aluminum, ammonia, benzathine, meglumine, methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2- diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, glucamine, methylglucamine, theobromine,purines, piperazine, piperidine, procaine, N-ethylpiperidine, theobromine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N- dimethylaniline, N-methylpiperidine, morpholine, N-methylmorpholine, N-ethylmorpholine, di cyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1 -ephenamine, N,N'- dibenzylethylenediamine or polyamine resins. In some embodiments, compounds as described herein may contain both acidic and basic groups and may be in the form of inner salts or zwitterions, for example, and without limitation, betaines. Salts as described herein may be prepared by conventional processes known to a person skilled in the art, for example, and without limitation, by reacting the free form with an organic acid or inorganic acid or base, or by anion exchange or cation exchange from other salts. Those skilled in the art will appreciate that preparation of salts may occur in situ during isolation and purification of the compounds or preparation of salts may occur by separately reacting an isolated and purified compound.

[0139] In some embodiments, compounds and all different forms thereof (e.g. free forms, salts, polymorphs, hydrates, hydrated salts, optical isomers, racemates, diastereoisomers, enantiomers, isomeric forms) as described herein may be in a solvent addition form, for example, solvates. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent in physical association with the compound or salt thereof. The solvent may be, for example, and without limitation, a pharmaceutically acceptable solvent. For example, hydrates are formed when the solvent is water and alcoholates are formed when the solvent is an alcohol.

[0140] In some embodiments, compounds and all different forms thereof (e.g. free forms, salts, solvates, isomeric forms) as described herein may include crystalline and amorphous forms, for example, polymorphs, pseudo-polymorphs, conformational polymorphs, amorphous forms, or a combination thereof. Polymorphs include different crystal packing arrangements of the same elemental composition of a compound. Polymorphs usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability and / or solubility. Those skilled in the art will appreciate that various factors including recrystallization solvent, rate of crystallization and storage temperature may cause a single crystal form to dominate.

[0141] In some embodiments, pharmaceutical compositions as described herein may comprise a salt of such a compound. Pharmaceutical preparations will typically comprise one or more carriers, excipients or diluents acceptable for the mode of administration of the preparation, be it by injection, inhalation, topical administration, lavage, or other modessuitable for the selected treatment. Suitable carriers, excipients or diluents (used interchangeably herein) are those known in the art for use in such modes of administration.

[0142] Suitable pharmaceutical compositions may be formulated by means known in the art and their mode of administration and dose determined by the skilled practitioner. For parenteral administration, a compound may be dissolved in sterile water or saline or a pharmaceutically acceptable vehicle used for administration of non-water soluble compounds such as those used for vitamin K. For enteral administration, the compound may be administered in a tablet, capsule or dissolved in liquid form. The tablet or capsule may be enteric coated, or in a formulation for sustained release. Many suitable formulations are known, including, polymeric or protein micro-particles encapsulating a compound to be released, ointments, pastes, gels, hydrogels, or solutions which can be used topically or locally to administer a compound. A sustained release patch or implant may be employed to provide release over a prolonged period of time. Many techniques known to one of skill in the art are described in Remington: The Science & Practice of Pharmacy by Alfonso Gennaro, 20th ed., Lippencott Williams & Wilkins, (2000). Formulations for parenteral administration may, for example, contain excipients, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, or hydrogenated naphthalenes. Biocompatible, biodegradable lactide polymer, lactide / glycolide copolymer, or polyoxyethylene polyoxypropylene copolymers may be used to control the release of the compounds. Other potentially useful parenteral delivery systems for modulatory compounds include ethylene vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes. Formulations for inhalation may contain excipients, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene 9 lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops, or as a gel.

[0143] Compounds or pharmaceutical compositions as described herein or for use as described herein may be administered by means of a medical device or appliance such as an implant, graft, prosthesis, stent, etc. Also, implants may be devised which are intended to contain and release such compounds or compositions. An example would be an implant made of a polymeric material adapted to release the compound over a period of time.

[0144] In some embodiments, an “effective amount” of a pharmaceutical composition as described herein includes a therapeutically effective amount or a prophylactically effective amount. A “therapeutically effective amount” refers to an amount effective, atdosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of a compound may vary according to factors such as the disease state, age, sex, and weight of the subject, and the ability of the compound to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. A therapeutically effective amount is also one in which any toxic or detrimental effects of the compound are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, a prophylactic dose is used in subjects prior to or at an earlier stage of disease, so that a prophylactically effective amount may be less than a therapeutically effective amount.

[0145] It is to be noted that dosage values may vary with the severity of the condition to be alleviated. For any particular subject, specific dosage regimens may be adjusted overtime according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions. The amount of active compound(s) in the composition may vary according to factors such as the disease state, age, sex, and weight of the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It may be advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage.

[0146] In general, compounds, as described herein, should be used without causing substantial toxicity. Toxicity of the compounds as described herein can be determined using standard techniques, for example, by testing in cell cultures or experimental animals and determining the therapeutic index, i.e., the ratio between the LD50 (the dose lethal to 50% of the population) and the LD100 (the dose lethal to 100% of the population). In some circumstances however, such as in severe disease conditions, it may be appropriate to administer substantial excesses of the compositions. Some compounds as described herein may be toxic at some concentrations. Titration studies may be used to determine toxic and non-toxic concentrations. Animal studies may be used to provide an indication if the compound has any effects on other tissues.

[0147] The disclosure may be further understood by the non-limiting examples. The following non-limiting examples are illustrative of the present disclosure:EXAMPLESI. Results and DiscussionExample 1: Luciferase assay showing Ha-pseudovirus entry inhibition by AkC and analogs.

[0148] The inhibition of Ha-pseudovirus entry by AkC and analogs (Scheme 2 shows AkC and analog 17, 19, 22 and 23 structures) was evaluated by luciferase assay (FIGs. 1-6).Scheme 2: AkC and selected analog structures.

[0149] Cells were pre-treated for 1 h with 200 nM of inhibitors (AkC analogs 17, 19, 22 and 23 were prepared in line with the procedures described in WO 2023 / 173232) before 18 h infection with Ha-pseudovirus, and viral entry was quantified by luciferase assay. Data are normalized to quantification of luciferase with only pseudo virus. Data is shown for IAV / H5Nl / Thailand / 2006 (FIG. 1), IAV / H5N1 / Texas 2024 (FIG. 2), Marburg virus (FIG. 3), Lassa vims (FIG. 4) and Chikungunya virus (FIG. 5) in comparison to SARS-CoV-2 Omicron JN1 (FIG. 6). Relative light unit (RLU, %) was calculated for assays where cells were treated using each of the compounds AkC, 17, 19, 22 and 23 depicted in Scheme 2 for each respective Ha-pseudovirus.Example 2: Dose-response curves of AkC against RSV and IAV / H1N1.Dose-response curves were generated for AkC in Calu-3 cells infected with RSV using dsRNA as an infection marker (FIG. 7). Dose-response curves were generated for AkC in Calu-3 cells infected with IAV / H1N1 / 2009 using dsRNA and IAV hemagglutinin (HA) as infection markers (FIG. 8). Alotaketal C (AkC) showed antiviral activity against RSVand IAV / H1N1. The antiviral activity of AkC was tested by dose-dependent reduction of RSV and IAV / H1N1 infection and validated using viral biomarkers of intracellular infection (dsRNA for RSV, and dsRNA and HA for IAV / H1N1, respectively). The EC50 values determined for the dsRNA for RSV and the dsRNA and HA for IAV / H1N1 can be seen in FIG. 7 and FIG. 8, respectively.Example 3: Dose-response curves of AkC analogs against IAV / H1N1.

[0150] Dose-response curves were generated for AkC analogs in Calu-3 cells infected with IAV / H1N1 / 2009 using dsRNA and IAV hemagglutinin (HA) as infection markers (FIGs. 9-11). Alotaketal C (AkC) analogs 19 and 23 (see Scheme 2 for structures) showed antiviral activity against IAV / H1N1. The antiviral activity of the AkC analogs was tested by dose-dependent reduction of IAV / H1N1 infection and validated using viral biomarkers of intracellular infection (dsRNA and IAV HA). Antiviral activity of Oseltamivir (FIG. 12), Baloxavir (Fig. 13), and EIDD-1931 (FIG. 14) were also measured for comparison. The EC50 values determined using dsRNA and HA for IAV / H1N1 can be seen in FIGs. 9-11. AkC analog 19 performed 10x better than FDA-approved neuraminidase inhibitor Oseltamivir in human Calu-3 lung cells, and 10x better than the broad-spectrum ribonucleoside analog EIDD-1931 against IAV / H1N1 infection (see EC50 data in FIGs. 11, 12 and 14 for AkC analog 19, Oseltamivir and EIDD-1931, respectively).Example 4: Dose- response curves of AkC analogs against Dengue virus.

[0151] Dose-response curves were generated for AkC analogs in human Huh 7.5.1 cells infected with Dengue virus serotype 2 (DENV2) using dsRNA and NS4B protein as infection markers (FIGs. 15-18). Alotaketal C (AkC) analog 19 (see Scheme 2 for structure) showed antiviral activity against DENV2. The antiviral activity of the AkC analogs was tested by dose-dependent reduction of DENV2 infection and validated using viral biomarkers of intracellular infection (dsRNA and NS4B protein). Antiviral activity of PKC inhibitors Go6983 (FIG. 19) and CRT0066854 (FIG. 20) were also measured for comparison. The EC50 values for the AkC analogs and PKC inhibitors determined using dsRNA and NS4B for DENV2 can be seen in FIGs. 15-20.Example 5: Dose- response curves of AkC analogs against Zika virus.

[0152] Dose-response curves were generated for AkC analogs in human Huh 7.5.1 cells infected with Zika virus (ZIKV) using dsRNA and NS4B protein as infection markers (FIGs. 21-24). Alotaketal C (AkC) analogs 19 and 23 (see Scheme 2 for structures) showed antiviralactivity against ZIKV. The antiviral activity of the AkC analogs was tested by dose-dependent reduction of ZIKV infection and validated using viral biomarkers of intracellular infection (dsRNA and NS4B protein). Antiviral activity of PKC inhibitors Go6983 (FIG. 25) and CRT0066854 (FIG. 26) were also measured for comparison. The EC50 values determined using dsRNA and NS4B for ZIKV can be seen in FIGs. 21-26.Example 6: Physiologically relevant cell-based system study of viral infection.

[0153] Compound AkC-19 reduced IAV H1N1 infection in air-liquid interface (ALI)- cultured primary human nasal epithelial cells (HNEpC; FIG. 27). Fully differentiated ALI cultures of HNEpC (MucilAir™ Pool nasal, EP02MP) were reconstituted using a mixture of nasal cells from 14 different healthy donors. ALI-cultured HNEpC were pretreated with the AkC- 17 and 19 at IpM, for 3 h at 37°C. The cultures were apically inoculated with MOI 1 IAV H1N1 and incubated for 2 h at 37°C. The apical chamber was washed with PBS, then the cultures were incubated for 48 h at 37°C. The cultures were fixed, and immunofluorescence staining was performed to detect influenza A non-structural protein 1 (NS1). Confocal images were acquired using a 63x / 1.40 oil objective lens on a Leica STELLARIS 5 microscope. Intracellular NS 1 levels were quantified using Imaris, averaged (four fields of view per membrane), and then normalized to DMSO-treated cells. One-way ANOVA using Dunneg’s multiple comparisons test was used to assess significance. Only P values less than 0.005 are shown (*** p < 0.0005).Example 7: Additional dose-response curves of AkC analogs against IAV / H1N1.

[0154] Dose-response curves were generated for AkC analogs 19 (see Scheme 2 for structure) and 24-28 (see Scheme 3 for structures; AkC analogs 24, 25, 27 and 28 were prepared in line with the procedures described in WO 2023 / 173232 and AkC analog 26 is a side product in the synthesis of AkC analogs 24 and 25 and was isolated from the same reaction product mixture that gives 24 and 25) in Calu-3 cells infected with IAV / H1N1 / 2009 using IAV hemagglutinin (HA) as infection markers (FIGs. 28-33).Scheme 3: Additional AkC analog structures.Alotaketal C (AkC) analogs 19, 24 and 26 showed antiviral activity against IAV / H1N1. The ECso values determined using hemagglutinin (HA) for IAV / H1N1 can be seen in FIGs. 28-33.Example 8: Dose-response curves of AkC analogs against IAV / H5N1.

[0155] Dose-response curves were generated for AkC analogs 17 and 19 (see Scheme 2 for structures) in Calu-3 cells infected with IAV / H5N1 / Texas 2024, and viral entry inhibition was quantified by luciferase assay (FIG. 34). Alotaketal C (AkC) analog 19 showed antiviral activity against IAV / H5N1. The EC50 values determined using nonlinear regression analysis for IAV / H5N1 can be seen in FIG. 34.II. Additional Discussion

[0156] It has been reported that certain AkC analogs had antiviral activity against coronavirus infection. It has now been described herein that AkC analogs 17, 19, 24 and 26 could block viral infection of an additional subset of authentic (live) human enveloped viruses, including influenza A viruses, RSV and flaviviruses in human cells. All these viruses usurp different attachment factors and entry receptors and encode for different structural and non-structural proteins. While not wishing to be limited by theory, the mechanism of action of AkC analogs in the lifecycles of these viruses includes blocking viral attachment / entry. This was demonstrated by using non-replicating pseudoviruses. The robustness of the inhibitory activity of the AkC analogs is variable across all the pseudoviruses tested in thesame cell line. This is consistent with the fact that all these human enveloped viruses usurp different attachment factors and entry receptors. While not wishing to be limited by theory, it is expected by the inventors that the AkC analogs may present specific mechanisms of action for each virus, despite being classified based on the results as “entry inhibitors”.

[0157] Alotaketal C (AkC) showed antiviral activity against RSV and IAV / H1N1. Alotaketal C (AkC) analogs, and in particular, AkC analog 19 (see Scheme 2 for structure) also showed antiviral activity against RSV, IAV / H1N1, Dengue virus serotype 2 (DENV2), and Zika virus. The antiviral activity of AkC and analogs thereof were tested by dosedependent reduction of RSV, IAV / H1N1, Dengue virus, and Zika virus infection and validated using viral biomarkers of intracellular infection (dsRNA for RSV, dsRNA and IAV hemagglutinin (HA) for IAV / H1N1, dsRNA and NS4B for Dengue virus, and dsRNA and NS4B for Zika virus, respectively). The ECso values determined for the dsRNA for RSV, dsRNA and HA for IAV / H1N1, dsRNA and NS4B for Dengue virus, and dsRNA and NS4B for Zika virus can be seen in FIG. 7, FIGs. 8-11, FIGs. 15-18, and FIGs. 21-24, respectively. AkC analog 19 (see Scheme 2 for structure) performed 10x better than FDA approved neuraminidase inhibitor Oseltamivir in human Calu-3 lung cells, and 10x better than the broad-spectrum ribonucleoside analog EIDD- 1931 against IAV / H1N1 infection. AkC analog 19 also performed well against Dengue virus and Zika virus infection versus PKC inhibitors. AkC analog 19 has also been validated against IAV / H1N1 (2009) using ALI (air-liquid interface) culture of patient-derived nasal cells, which is the gold standard for influenza A virus drug testing. Also reported herein is data demonstrating efficacy of new AkC analogs 24 and 26 (see Scheme 3 for structures) against pandemic H1N1 (2009) in human lung cells. In contrast, AkC analogs 25, 27 and 28 were inactive against H1N1 in Calu-3 cells. Also reported herein is an ED50 curve for AkC analog 19 against the pseudo virus encoding for the Avian highly pathogenic H5N1 / TX / 2024. The EC50 value is 1.3 nM.III. General Methods

[0158] Median effective dose (ECso) curves (for AkC and analogues in Calu-3 and Huh 7.5.1 cells infected with RSV, IAV / H1N1, DENV or ZIKV): Cells were seeded in 96- well plates the day before infection (104cells / well). Virus stocks were diluted in cell-specific media to a multiplicity of infection (MOI), according to each virus, without antibiotics. Cells were pretreated with compounds for 3 h and then incubated with the virus for 48 h, followed by fixation of the cells with 3.7% formalin for 30 min to inactivate the virus. The fixative wasremoved, and the cells were washed with phosphate-buffered saline (PBS), permeabilized with 0.1% Triton X-100 for 10 min and blocked with 1% bovine serum albumin (BSA) for 1 h at room temperature. This was followed by immunostaining with primary antibodies at working dilutions of 1:1000 overnight at 4°C. Secondary antibodies were used at a 1:2000 dilution, they included the goat anti-mouse IgG Alexa Fluor 488 and goat anti-rabbit IgG Alexa Fluor 555 with the nuclear stain Hoechst 33342 at 1.5 pg / mL for 1 h at room temperature in the dark. After washing with PBS, the plates were kept in the dark at 4°C until imaging was performed on a high-content screening (HCS) platform (Celllnsight CX7 HCS, Thermo Fisher Scientific) with a 10* objective. Intracellular dose response (ECso values) of AkC against RSV and AkC and analogs against IAV / H1N1 were determined by pre-treating Calu-3 cells for 3 h with serially diluted compounds, followed by viral infection for 48 h. Viral infection was detected by staining for dsRNA or human influenza hemagglutinin (HA) protein signal and quantified as described above. ECso experiments were repeated at least three times for each compound with two technical replicates in each experiment. Intracellular HA and dsRNA levels were interpolated to negative control (0.1% dimethyl sulfoxide (DMSO), no infection) = 0, and positive control (0.1% DMSO, with infection) = 100. The GraphPad Prism 11™ (GraphPad Software, Inc.) nonlinear regression fit modelling variable slope was used to generate a dose-response curve [Y = Bottom + (Top- Bottom) / (l+10A((LogIC5o-X)*Hillslope)], constrained to top = 100, bottom = 0. Intracellular dose response (ECso values) of AkC analogs against Dengue and Zika were determined by pre-treating Huh 7.5.1 cells for 3 h with serially diluted compounds, followed by viral infection for 48 h. Viral infection was detected by staining for dsRNA or NS4B protein signal and quantified as described above. ECso experiments were repeated twice for each compound for Dengue and once for each compound for Zika. Intracellular non-structural protein 4B (NS4B) and dsRNA levels were interpolated to negative control (0.1% DMSO, no infection) = 0, and positive control (0.1% DMSO, with infection) = 100. The GraphPad Prism 11™ (GraphPad Software, Inc.) nonlinear regression fit modelling variable slope was used to generate a dose-response curve [Y = Bottom + (Top-Bottom) / (l+10A((LogIC5o- X)*Hillslope)], constrained to top = 100, bottom = 0.

[0159] Ha-PV(luc) entry inhibition assay: The viral entry studies were based on a hybrid alphavirus-particle, a non-replicative particle, developed by Virongy Bioscience, composed of all the structural proteins of the virus, and also contains a genome derived from an alphavirus-based vector, which can rapidly and robustly express reporter genesafter viral entry. Cells were seeded (2* 104cells / well) in a 96-well white cell culture-treated. A 2 h pre-treatment was performed in media without fetal bovine serum (FBS) or 200 nM of compound (AkC or analogues). A normalized preparation of Ha-PV(luc)(from Virongy Bioscience) was then added to wells. Infection proceeded for 18 h and luminescence was detected on the SpectraMax Gemini XS spectrofluorometer (Molecular Devices, LLC) between 550-570nm with a read time of 0.3 seconds / well.

[0160] Design of the Ha-H5N1 vector: Modified from Hetrick et.al 2022. The vector contains an RSV promoter that transcribes the full-length viral RNA genome to be packaged into Ha-H5N1 particles. Shown in FIG. 35 is the 5' untranslated region followed by openreading frames coding for nonstructural proteins (nsps) 1-4 from Smiliki Forest virus (SFV), viral subgenomic promoters for Luc or RFP reporter expression, the 3' untranslated region, and a poly(A)tail that is self-cleaved by the hepatitis virus ribozyme (RZ). The A / Texas / 37 / 2024 H5N 1 -packaging signal is inserted in front of the 3' untranslated region. To assemble viral particles, HEK293T cells were co-transfected with Ha-H5N1 and the vectors expressing the 5 structural proteins of A / Texas / 37 / 2024 H5N1 (HA, NA, Ml, M2 andN).

[0161] Characterization of AkC analog 26 enantiomers: FIG. 36 shows a high resolution mass spectrum (M + H)+, FIG. 37 shows a ID proton NMR spectrum (600 MHz - 0 to 8 ppm) and FIG. 38 shows a ID carbon NMR spectrum (150 MHz - 0 to 160 ppm) for the mixture of the enantiomers of AKC -26. The NMR spectra were recorded in benzene-dg.

[0162] While the disclosure has been described with reference to what are presently considered to be the preferred examples, it is to be understood that the disclosure is not limited to the disclosed examples. To the contrary, the present disclosure is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Although various embodiments of the invention are disclosed herein, many adaptations and modifications may be made within the scope of the invention in accordance with the common general knowledge of those skilled in this art. Such modifications may include, for example, the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Although the description herein contains many specific examples, these should not be construed as limiting the scope of the disclosure but as merely providing illustrations of some of the embodiments of the disclosure. For example, the scope of the disclosure should be determined by the appended aspects and their equivalents, rather than by the examplesgiven. Every formulation or combination of components described or exemplified herein may be used to practice the disclosure, unless otherwise stated.

[0163] All publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Where a term in the present application is found to be defined differently in a document incorporated herein by reference, the definition provided herein is to serve as the definition for the term. Citation of references herein is not an admission that such references are prior art to an embodiment of the present invention.FULL CITATIONS FOR DOCUMENTS REFERRED TO IN THE DESCRIPTIONAshhurst et al., Potent anti-SARS-CoV-2 activity by the natural product gallinamide A and analogues via inhibition of cathepsin L. Journal of Medicinal Chemistry 65.4 (2021): 2956-2970.Beans, E.J. et al. 2013 Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo. Proc Natl Acad Sci U S A. 2013 Jul 16; 110(29): 11698- 703. doi: 10.1073 / pnas.1302634110. Epub 2013 Jun 28.Blagojevic et al., Synthetic Analogs of the Sponge Sesterterpenoid Alotaketal C are Potent Inhibitors of SARS-CoV-2 Omicron BA.l and BA.5 Infections of Human Lung Cells. Org. Lett. 2023, 25, 26, 4825-4829.Costa da Silveira Oliveira et al. 2017 Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses. Molecules. 2017 Mar 22; 22(3):505. doi: 10.3390 / molecules22030505.Hetrick et al., Development of a hybrid alphavirus-SARS-CoV-2 pseudovirion for rapid quantification of neutralization antibodies and antiviral drugs. Cell Rep Methods. 2022 Mar 28;2(3): 100181. doi: 10.1016 / j.crmeth.2022.100181.Mani et al., Natural product-derived phytochemicals as potential agents against coronaviruses: A review, Virus Research, Volume 284, 2020, 197989.Moghadamtousi, S.Z. et al. 2015. Potential antiviral agents from marine fungi: an overview. Mar. Drugs 13, 4520-4538.Musarra-Pizzo, M. et al. 2021. Antiviral activity exerted by natural products against human viruses. Viruses 2021,13(3), 828.Olivera et al., Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses. Molecules 2017, 22(3), 505.Wang, S.X. et al. 2014. Potential anti-HPV and related cancer agents from marine resources: an overview. Mar. Drugs 12, 2019-2035.Wang, M. et al. 2016. Sesterterpenoids isolated from the sponge phorbas sp. activate latent HIV-1 provirus expression. J. Org. Chem. 81, 11324-11334.

Claims

CLAIMSWhat is claimed is:

1. A use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, C3- locycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or C3- locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor 0Rfor Rband Rcjointly form =C RsRh:Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by aheteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, Cs-iocycloalkenyl or C3-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, for treatment of a viral infection caused by one or more of a Kilrinoviricola virus and a Negarnaviricola virus, in a subject in need thereof.

2. A use of a compound of Formula (I):wherein represents a single bond or a double bond;X3is =0, S, N-OH, N-NH-R61or O-Re2;X4is O or S;X5is O or absent;Rais H, Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3- locycloalkenyl or C3-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3-iocycloalkenyl or C3. locycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci- walkyl, C2-ioalkenyl, C2-ioalkynyl, C3-iocycloalkyl, C3-iocycloalkenyl or C3. locycloalkynyl is optionally substituted;Rband Rcare each independently H, Rfor 0Rfor Rband Rcjointly form =C RsRh;Rdis H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3. 2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl wherein one or more available carbon atoms in the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3- 2ocycloalkenyl or C3-2ocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-2ocycloalkyl, C3-2ocycloalkenyl, C3-2ocycloalkynyl, aryl or heteroaryl is optionally substituted;Rel, Re2, Rgand Rhare each independently H, Ci-ioalkyl, C2-ioalkenyl, C2- walkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl, wherein one or more available carbon atoms in the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, C3- locycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is / are optionally replaced by a heteroatom; and wherein the Ci-ioalkyl, C2-ioalkenyl, C2-ioalkynyl, Cs-iocycloalkyl, Cs-iocycloalkenyl or Cs-iocycloalkynyl is optionally substituted; andRfis H, CH3, C(=O)CH3or C(=O)CH2CH(CH3)CH3, or a pharmaceutically acceptable salt, solvate and / or prodrug thereof, in the preparation of a medicament for treatment of a viral infection caused by one or more of a Kitrinoviricota virus and aNegarnaviricola virus, in a subject in need thereof.

3. The use of claim 1 or 2, wherein X is absent, and the compound of Formula (I) is a compound of Formula 1(a):1(a)5 wherein Re2, R4, Ra, Rb, Rcand Rdare as defined in claim 1.

4. The compound of claim 3, wherein Re2is unsubstituted Ci-ealkyl.

5. The compound of claim 4, wherein Re2is methyl.

6. The use of claim 1 or 2, wherein X is O, and the compound of Formula (I) is a compound of Formula 1(b):Kb) wherein X3, R4, Ra, Rb, Rcand Rdare as defined in claim 1.

7. The use of claim 6, wherein the compound of Formula 1(b) has the following stereochemistry:

8. The use of any one of claims 1 to 7, wherein X3and X4are O.

9. The use of any one of claims 1 to 8, wherein Rais H.

10. The use of any one of claims 1 to 9, wherein Rband Rcare H.

11. The use of any one of claims 1 to 9, wherein Rbis AcO and Rcis CH3.

12. The use of any one of claims 1 to 11, wherein Rdis unsubstituted Cs-i2alkyl or Cs-i2alkenyl.

13. The use of any one of claims 1 to 11, wherein Rdis -(CH2)nCHCH2, wherein n is an integer from 4 to 12.

14. The use of claim 1 or 2, wherein the compound of Formula (I) is selected from:

15. The use of claim 14, wherein the compound of Formula (I) has the structure:

16. The use of claim 1 or 2, wherein the compound of Formula (I) has the structure:

17. The use of any one of claims 1 to 16, wherein the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is for use in the form of a pharmaceutical composition comprising the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof and optionally a pharmaceutically acceptable excipient.

18. The use of any one of claims 1 to 17, wherein the compound of Formula (I) or the pharmaceutically acceptable salt, solvate and / or prodrug thereof is in the form of the compound of Formula (I).

19. The use of any one of claims 1 to 18, wherein the viral infection is caused by a fdovirus, an orthomyxovirus, an arenavirus, a togavirus, a flavivirus, a pneumovirus or combinations thereof.

20. The use of any one of claims 1 to 19, wherein the viral infection is caused by Marburg virus, influenza virus, Lassa virus, chikungunya virus, dengue virus, Zika virus, respiratory syncytial virus or combinations thereof.

21. The use of claim 20, wherein the viral infection is caused by Marburg virus.

22. The use of claim 20, wherein the viral infection comprises infection with a combination of influenza virus and respiratory syncytial virus.

23. The use of claim 20, wherein the viral infection is caused by influenza virus.

24. The use of claim 20, 22 or 23, wherein the influenza virus is an influenza A virus (IAV).

25. The use of claim 20, wherein the viral infection is caused by respiratory syncytial virus.

26. The use of claim 20, wherein the viral infection is caused by Lassa virus.

27. The use of claim 20, wherein the viral infection is caused by chikungunya virus.

28. The use of claim 20, wherein the viral infection is caused by dengue virus.

29. The use of claim 20, wherein the viral infection is caused by Zika virus.

30. The use of any one of claims 1 to 29, wherein the subject is a human.

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