Compositions Comprising Eukaryotic Microalgae or Extracts Thereof for Use in Treating Viral Diseases - Patent application

Abstract

Compositions comprising eukaryotic microalgae or extracts thereof for use in the treatment of viral diseases are provided. Compositions comprising eukaryotic microalgae or extracts thereof may be of use in the treatment of viral diseases (e.g., coronaviruses) and as inhibitors of binding of the spike protein receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2). Compounds derivable from eukaryotic microalgae may also be of use in the treatment of viral diseases. As a result, eukaryotic microalgae may be used as antiviral agents.

Description

[Technical field]

[0001] The present invention relates to a composition comprising eukaryotic microalgae or an extract thereof. More specifically, the present invention relates to a composition comprising eukaryotic microalgae or an extract thereof for use in the treatment of viral diseases, a compound derivable from eukaryotic microalgae for use in the treatment of viral diseases, a composition comprising eukaryotic microalgae or an extract thereof for use as an inhibitor of the binding of spike protein receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2), and the use of eukaryotic microalgae or an extract thereof as an antiviral agent. [Background technology]

[0002] Viruses are small infectious agents that only replicate in the living cells of other organisms.Viruses can infect a variety of life forms, from animals and plants to microorganisms (including bacteria and archaea).Viral infections typically cause disease symptoms in affected subjects, which can vary from mild symptoms to severe symptoms, and can result in morbidity and mortality.

[0003] Some of the most common symptoms associated with viral infections are due to human respiratory diseases. Examples of human respiratory diseases resulting from viruses include influenza caused by various influenza viruses, severe acute respiratory syndrome (SARS) caused by coronavirus (SARS-CoV), respiratory diseases that may be caused by adenoviruses, and bronchitis and childhood pneumonia caused by respiratory syncytial virus (RSV).

[0004] Coronavirus disease 2019, commonly known as "COVID19," is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing pandemic with over 88 million confirmed cases worldwide and over 1.89 million deaths as of March 2021. Mortality is highest among older adults and others with underlying health problems. While most people develop mild symptoms, some people develop severe symptoms such as pneumonia, respiratory failure, shock, or multiple organ dysfunction.

[0005] The high mortality rate in patients presenting to the critical care with severe acute SARS-CoV-2 infection is attributed to a combination of a hyperinflammatory syndrome, coagulopathy, and pathological activation of immunological pathways leading to cytokine release syndrome.

[0006] There is an urgent need for effective early treatments with both antiviral and disease-modifying properties to limit the pressure that severe COVID-19 cases place on the healthcare infrastructure. While vaccination remains the most effective means of primary prevention of SARS-CoV-2 infection, intranasal or intraoral delivery of antivirals may be an important additional approach to prevent infection and spread of SARS-CoV-2 and other respiratory viruses.

[0007] Typically, SARS-CoV-2 spreads primarily through exposure to aerosols from infected people when they breathe, cough, sneeze, or speak. Hence, one of the main points of entry of the SARS-CoV-2 virus into the human body is through the mouth, nose, or eyes. Being able to pharmacologically block these points of entry may help reduce the number of COVID-19 cases. When the virus enters a subject through the subject's mouth, nose, or eyes, it replicates by attaching to the host cell surface before entering the cell. The spike protein receptor-binding domain (RBD) recognizes and attaches to the angiotensin-converting enzyme 2 (ACE2) receptor found on the surface of type I and type II pneumocytes, endothelial cells, and ciliated bronchial epithelial cells. ACE2 is an exopeptidase that catalyzes the conversion of angiotensin II to angiotensin 1-7 and L-phenylalanine. Angiotensin II is part of the classical renin-angiotensin system (RAS), a hormonal system that regulates fluid balance and blood pressure, and maintains vascular tone. ACE2 has also been proven to be the primary receptor for the entry of respiratory viruses such as human respiratory coronavirus NL63, SARS-coronavirus (SARS-CoV), and other SARS-CoV-2 variants such as the new B117. Binding of SARS-CoV and SARS-CoV-2 to ACE2, followed by membrane fusion and viral entry into the cell, is linked to downregulation of the ACE2 receptor. This downregulation of ACE2 also impairs its pivotal protective function, the degradation of angiotensin II to angiotensin 1-7. Angiotensin II is associated with a variety of adverse health outcomes, including cardiovascular disease, enhanced inflammation in response to oxidative stress, and hypercoagulation. In addition, angiotensin II is also a macrophage activator that leads to increased secretion of IL-6 and TNFα, as well as other inflammatory responses.The ACE2 receptor opposes angiotensin II by degrading (and thus clearing) it and by catalyzing its conversion to angiotensin II 1-7, resulting in several positive and even antagonistic effects on angiotensin II. Although selective ACE2 inhibitors exist, such as MLN-4760, which may inhibit cell attachment of viruses such as SARS-CoV-2, they also block the degradation of angiotensin II to angiotensin 1-7. Summary of the Invention

[0008] Therefore, there is a need for new therapeutic approaches that block viral entry via the SARS-CoV-2 RBD without inhibiting ACE2.

[0009] The present invention provides compositions comprising eukaryotic microalgae or extracts thereof for use in the treatment of viral diseases.

[0010] The term "treatment" as used herein may include preventative (prophylactic) treatment, curative treatment, maintenance treatment, and promotive treatment.

[0011] Surprisingly, it has been found that compositions comprising eukaryotic microalgae or extracts thereof have a beneficial effect in preventing the spread of viral diseases, such as COVID-19.

[0012] The viral disease may be a respiratory viral disease. The viral disease may be caused by one or more of influenza virus, respiratory syncytial virus (RSV), parainfluenza virus, or respiratory adenovirus. The viral disease may be severe acute respiratory syndrome (SARS). The viral disease may be MERS and / or COVID-19. The viral disease may be caused by a SARS-related virus. The viral disease may be caused by a coronavirus (SARS-CoV-2), where coronavirus is understood to include the orthocoronavirus subfamily within the Coronaviridae family.

[0013] More specifically, it has been found that compositions comprising eukaryotic microalgae or extracts thereof may inhibit viral spike protein receptor binding domain (RBD) binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Advantageously, compositions comprising eukaryotic microalgae or extracts thereof do not affect ACE2 activity. As a result, compositions comprising eukaryotic microalgae or extracts thereof do not impair respiratory system function or lead to cardiovascular disease, heightened inflammation in response to oxidative stress, or hypercoagulation. Advantageously, the compositions prevent viral diseases from reaching the brain or bronchi and lungs. Therefore, the compositions of the present invention may be used to inhibit or prevent the respiratory system from being compromised. Furthermore, by preventing the establishment of viral infection of olfactory epithelial cells and gingival epithelial cells, where the viral infection can attack the respiratory center and migrate to the central nervous system to affect neurons, the compositions of the present invention may also prevent SARS-CoV-2 infection from causing loss of smell.

[0014] In an alternative embodiment, the present invention may relate to prokaryotic microalgae or extracts thereof. Aspects of the present invention described with respect to eukaryotic microalgae or extracts thereof may equally be applied to the prokaryotic microalgae or extracts thereof of the present invention. In particular, the present invention may relate to compositions comprising prokaryotic microalgae or extracts thereof for use in treating viral diseases. Prokaryotic microalgae may include cyanobacteria (previously known as "blue-green algae").

[0015] The term "eukaryotic microalgae" is understood to mean a diverse group of aquatic organisms capable of performing photosynthesis. Eukaryotic microalgae are single-celled species that exist individually or in chains or groups. Eukaryotic microalgae may include Chlorophyta, Phaeophyta, and Red Algae. More specifically, eukaryotic microalgae may include the phyla Rhodophyta (red algae), Chlorophyta (green algae), and Phaeophyta (brown algae). Eukaryotic microalgae may be of the genus Nannochloropsis or Tetraselmis.

[0016] Preferably, the eukaryotic microalgae may be green eukaryotic microalgae, for example green eukaryotic microalgae with the ability of photosynthesis. The eukaryotic microalgae may be of the phylum Chlorophyta, preferably Chlorella. The term "Chlorella" is understood to refer to the genus of unicellular eukaryotic green algae belonging to the phylum Chlorophyta. Advantageously, Chlorella is a generally recognized as safe (GRAS) substance by the FDA.

[0017] Preferably, the eukaryotic microalgae may be selected from one or more of Chlorella autotrophica, Chlorella colonials, Chlorella lewinii, Chlorella minutissima, Chlorella pituita, Chlorella pulchelloides, Chlorella pyrenoidosa, Chlorella rotunda, Chlorella singularis, Chlorella sorokiniana, Chlorella variabilis, Chlorella volutis, Chlorella vulgaris, Tetraselmis Chuii, Nannochloropsis gaditana.

[0018] More preferably, the composition may comprise a eukaryotic microalgae or an extract thereof for use in the treatment of a viral disease caused by the coronavirus SARS-CoV-2, wherein the eukaryotic microalgae is Chlorella.

[0019] Surprisingly, it has been found that a composition comprising Chlorella or an extract thereof may have beneficial effects in the treatment of COVID-19. More specifically, it has been found that Chlorella may inhibit viral RBD binding to the ACE2 receptor without affecting ACE2 activity. Therefore, a composition comprising Chlorella or an extract thereof may be used in the treatment of SARS-CoV-2 infection and COVID-19.

[0020] Additionally, Chlorella has been found to prevent viruses from binding to the ACE2 receptors present on cells in the mouth, nose, and / or eyes. By preventing viral disease from binding to these cell surfaces, Chlorella inhibits the ability of viral disease to enter and replicate in cells, and also prevents further infection from viral disease particles released by already infected cells.

[0021] The extract of eukaryotic microalgae may include one or more of proteins, lipids, vitamins, minerals, folate, iron, fiber, and / or pigments. The vitamins may include vitamin B and vitamin D12.

[0022] The protein may be selected from one or more of plastocyanin (A0A2P6TGD1), glycine-rich 2 (A0A2P6TDY2), SMAD FHA domain containing (A0A2P6U3K7), chloroplast thylakoid lumen kDa (A0A2P6TNZ5), peptidyl prolyl isomerase (A0A2P6TGB0), calmodulin (A0A2P6TFR8), 10 kDa chaperonin-like (A0A2P6THP7), membrane isoform A (A0A2P6TEF6), L-induced nipper (A0A2P6TU12), beta-Ig-H3 fasciclin (A0A2P6TQQ9).

[0023] The pigment may be chlorophyll. The chlorophyll may be one or more of chlorophyll a, chlorophyll b, chlorophyll c1, chlorophyll c2, chlorophyll d, chlorophyll f. Preferably, the extract may include chlorophyll c1 and / or c2, which are prevalent in many algae. The extract may include precursors of chlorophyll, such as precursors derived from glutamate.

[0024] The extract of eukaryotic microalgae may contain natural or synthetic chlorophyll. Advantageously, synthetic chlorophyll is registered as a food additive colorant (E140) and is therefore safe for use in food.

[0025] The composition comprising eukaryotic microalgae or an extract thereof for use in the treatment of viral diseases may be administered locally. Preferably, the composition according to the present invention may be administered topically. The composition may be a powder, liquid, aerosol, gel, paste or cream. The composition may be administered to the nasal or oral cavity. Preferably, the composition according to the present invention may be administered as a nasal spray, mouthwash, or oral inhalation formulation. Local administration to the respiratory tract is desirable because it helps to maintain a high local concentration of eukaryotic microalgae or an extract thereof at the primary site of infection (e.g., airway respiratory epithelium) while keeping the systemic burden low compared to systemic administration. Advantageously, this has a dual benefit: first, the composition administered as a nasal spray or mouthwash may stop viral infection via the nasal and oral cavities in healthy subjects by shielding the epithelial cells of the nasal and oral mucosa, and second, in the case of newly diagnosed infected subjects, the composition administered as a nasal spray or mouthwash may limit or prevent viral particles released by dying cells from colonizing new cells (such as olfactory epithelium, gingival epithelium, etc.). Limiting and / or preventing further colonization prevents the virus from spreading to new pathways, such as the cardiovascular system, and / or from infecting more cells of the respiratory epithelium or lower respiratory system.

[0026] Compositions according to the invention may comprise at least about 0.001 μg / mL, at least about 0.01 μg / mL, at least about 0.1 μg / mL, at least about 1 μg / mL of eukaryotic microalgae or an extract thereof.

[0027] Compositions according to the present invention may comprise about 10000 μg / mL or less, about 1000 μg / mL or less, about 100 μg / mL or less, about 10 μg / mL or less of eukaryotic microalgae or an extract thereof.

[0028] The composition according to the present invention may contain from about 0.001 μg / mL to about 10,000 μg / mL, from about 0.01 μg / mL to about 1,000 μg / mL, from about 0.1 μg / mL to about 100 μg / mL, or from about 1 to about 10 μg / mL of eukaryotic microalgae or an extract thereof.

[0029] The composition comprising the eukaryotic microalgae or an extract thereof may include any range from a given endpoint. The composition comprising the eukaryotic microalgae or an extract thereof may allow for an effective dose of the extract for use in treating, for example, a viral disease.

[0030] The present invention also provides compounds derivable from eukaryotic microalgae for use in the treatment of viral diseases. The term "compound derivable from eukaryotic microalgae" as used herein is understood to mean that the compound may be isolated or extracted from microalgae, for example, the compound may be isolated or extracted from a culture of microalgae. Conventional methods for isolating or extracting compounds from microalgae are available to those skilled in the art, for example in the form of commercially available kits for isolating or extracting compounds from microalgae. The term "compound derivable from eukaryotic microalgae" may also include chemically synthesized compounds that are naturally present in eukaryotic microalgae and therefore may be "derived" from eukaryotic microalgae by conventional methods.

[0031] The present invention also provides a composition comprising eukaryotic microalgae or an extract thereof for use as an inhibitor of the binding of spike protein receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2).Preferably, the composition comprises eukaryotic microalgae or an extract thereof for use as an inhibitor of the binding of RBD to ACE2 in vivo.For example, the composition comprises eukaryotic microalgae or an extract thereof for use as an inhibitor of the binding of RBD to ACE2 in a human subject.

[0032] Preferably, the composition comprising the eukaryotic microalgae or an extract thereof is for use as an inhibitor of RBD binding to ACE2 without affecting ACE2 activity.

[0033] The present invention provides compositions comprising eukaryotic microalgae or extracts thereof for use in the treatment of viral diseases and / or as inhibitors of binding of spike protein receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) to provide a reduction in adverse events, which may include, but are not limited to, adverse events caused by excess of angiotensin II, such as dyspnea, cardiovascular events, inflammatory responses, such as inflammation in response to oxidative stress, thrombosis with thrombocytopenia, hypercoagulation, such as disseminated intravascular coagulation (DIC).

[0034] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which: [Brief description of the drawings]

[0035] [Figure 1] FIG. 1 is an image of a protein gel showing Chlorella extract. [Diagram 2] Figures 2A and 2B show the inhibition of ACE2:SARS-CoV-2 spike binding, as measured by chemiluminescence, using various concentrations of Chlorella extract [MIX0000036] (Figure 2A) and the positive control EDTA (Figure 2B). [Diagram 3] FIG. 3 shows the activity of ACE2 in the presence of Chlorella extract. [Figure 4] Figure 4 shows the effect of Chlorella extract and Remdesivir on infection of Vero E6 cell cultures with active SARS-CoV-2. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Experiment 1 - Proteomic characterization The following experiments were carried out with a Chlorella extract obtained from Algosource (Saint-Nazaire, France), which showed the greatest homogeneity with Chlorella sorokiniana after proteomic analysis.

[0037] The proteome of Chlorella extracts was assessed by microfluidic electrophoresis (LabChip protein characterization system) and by liquid chromatography coupled to mass spectrometry (LC-MS / MS) in data-dependent acquisition mode (protein profiling).

[0038] Microfluidic electrophoresis demonstrated the highest abundance of proteins in the low molecular weight range. Figure 1 is an image of a protein gel confirming that proteins below 20 kDa have the highest abundance.

[0039] Total protein abundance measurements by LC-MS using a data-dependent acquisition approach confirmed these observations (Table 1). Table 1 contains a list of the most abundant proteins with their accession numbers and normalized spectral abundance factor (NSAF) scores. Spectral count analysis demonstrated that several proteins involved in photosynthesis were particularly abundant. [Table 1]

[0040] Experiment 2 - Inhibitor screening assay Following the standard ACE2:SARS-CoV-2 spike inhibitor screening assay protocol (BPSBioscience, San Diego, USA), the assay plate was coated with ACE2-His solution (1 μg / mL) for 1 h at room temperature (RT). The ACE2-His coating solution was washed off to keep only ACE2-His coated on the assay plate. The assay plate was incubated with blocking buffer for 10 min to obtain specific binding of the spike. After removing the blocking buffer, various concentrations of Chlorella extract ranging from 0.001 to 100 μg / mL were incubated for 1 h, followed by initiating the binding reaction using SARS-CoV-2 spike (20 ng / well) solution. The mixture was incubated for another 1 h at room temperature, then washed and blocked again for 10 min. Finally, the plate was incubated with secondary HRP-labeled antibody solution (1:1000) against SARS-CoV-2 spike for 1 h at room temperature. The HRP-labeled antibody was washed off and chemiluminescence was initiated and measured using an enhanced chemiluminescence substrate and a FLUOstar Omega plate reader (BMG Labtech).

[0041] To characterize the effect of Chlorella extract on ACE2:SARS-CoV-2 binding, we used a commercially available recombinant SARS-CoV-2 spike inhibitor screening assay (BPSBioscience, San Diego, USA), designed for screening and profiling inhibitors.

[0042] Figure 2A demonstrates that Chlorella extract has a dose-dependent inhibition of ACE2 binding to SARS-CoV-2. As a result, this indicates that the primary entry of the virus into the cell is blocked. More specifically, Figures 2A and 2B show the inhibition of ACE2:SARS-CoV-2 spike binding measured by chemiluminescence using various concentrations of (Figure 2A, MIX0000036, Chlorella extract) and the positive control EDTA (Figure 2B).

[0043] ACE2:SARS-CoV-2 spike binding was measured in relative light units (RLU). The half maximal inhibitory concentration (IC50) was determined, which was IC50=16.58 μg / mL for Chlorella extract. Figure 2B confirms that such an assay works. As a negative control, no SARS-CoV-2 spike was applied (negative). As a positive control, 1 ng / μL of SARS-CoV-2 spike was applied (positive). Ethylenediaminetetraacetic acid (EDTA) was used to confirm ACE2:SARS-CoV-2 spike binding in the test range of 0.45 μm to 1000 μm.

[0044] Experiment 3 – No interference with the catalytic pathway of ACE2 To characterize the effect of Chlorella extract on ACE2 enzymatic activity, we used a cellular assay that monitors the catalytic activity of ACE2 using a fluorescent ACE2 substrate to demonstrate successful inhibition by loss of fluorescence.

[0045] The ACE2 enzyme activity assay was designed to measure the exopeptidase activity of ACE2 and to screen for inhibition. Activity was measured using commercially available synthetic fluorescent substrates for ACE2 and rACE2 (R&D Systems, Zug, Switzerland). rACE2 was used to generate a standard curve using assay buffer, 75 mM TRIS, 1 M NaCl, ph 7.5. Natural extract screening was performed using 100 ng / mL rACE2 and 15 μM ACE2 fluorescent substrate, and various concentrations of Chlorella extract. The mixture was then incubated at 37°C for 1 hour and measured at excitation 320 nm and emission 405 nm using a Flexstation 3 (Molecular Devices, San Jose, CA, USA).

[0046] Chlorella extract in the range of 4.5 μg / mL to 10,000 μg / mL showed no effect on ACE2 enzyme activity, indicating that the main function of ACE2, which degrades angiotensin II to angiotensin 1-7, was maintained (Figure 3). As a positive control, a known ACE2 inhibitor (MLN-4760) in the range of 0.045 nM to 11,100 nM was used. More specifically, Figure 3 shows the activity of the catalytic pathway of ACE2 measured by fluorescence in the presence of various concentrations of Chlorella extract (MIX0000036, Figure 3A), and the positive control, MLN-4760 (Figure 3B), where RFU is relative fluorescence unit. The half-maximal inhibitory concentration (IC50) of MLN-4760 was 0.19 nM.

[0047] Experiment 4 - Chlorella extract protects cells from infection against active SARS-CoV-2. To characterize the protective effect of Chlorella extract on the vulnerability of Vero E6 cells to infection by SARS-CoV-2, a virus neutralization assay monitoring cell viability was performed.

[0048] Viral suspensions containing 200 TCID50 doses of SARS-CoV-2 were prepared for different concentrations of Chlorella and Remdesivir in a final volume of 200 μL. The resulting viral suspensions were incubated at 37°C for 1 hour in a transport box containing a CO2 bag and H2O.

[0049] Vero E6 cells were grown to confluency in MEM (M3303), 1.25% L-glutamine, 1% P / S, 1% NEAA, Bicarbonat, 10% FCS (all Bioswisstec, Switzerland) according to the manufacturer's procedure. Cells were then seeded at 200,000 cells / well in 96-well plates. Infection of Vero E6 cells was performed by removing the cell medium from the cell suspension and adding 200 μL of the prepared virus suspension. The cell suspension containing Vero E6 with SARS-CoV-2 / Chlorella / Remdesivir was incubated for 4 days at 37 °C in a transport box containing a CO2 bag and H2O. After incubation, Vero E6 cells were measured using Celltiter Glo (Promega) according to the manufacturer's procedure and also measured using a GloMax plate reader (Promega).

[0050] Figure 4 shows the antiviral activity of Chlorella extract (MIX0000036, open circles) using active SARS-CoV-2 (French isolate) and VeroE6 cells. Viral fusion in VeroE6 cells occurs primarily after ACE2 binding followed by endocytosis. Pretreatment of Chlorella extract through the tested concentrations of 63 μg / mL to 2000 μg / mL prior to SARS-CoV-2 infection inhibited SARS-CoV-2 viral entry over 72 hours with an IC50 of approximately 140 μg / mL in VeroE6. In the presence of Chlorella extract, Vero E6 cell viability following SARS-CoV-2 infection peaked at 250 μg / mL.

[0051] As a positive control, we used the broad-spectrum antiviral drug remdesivir (Figure 4, filled circle), which blocked SARS-CoV-2 replication over the tested range of 0.04 μg / mL to 10 μg / mL by halting viral RNA synthesis.

Claims

1. A composition comprising a eukaryotic microalgae or an extract thereof for use in the treatment of a viral disease.

2. 2. The composition of claim 1, wherein the viral disease is Severe Acute Respiratory Syndrome (SARS).

3. The composition of claim 1 , wherein the viral disease is caused by a SARS-related virus.

4. The composition of claim 1, wherein the viral disease is caused by a coronavirus (SARS-CoV-2).

5. The composition of claim 1 , wherein the eukaryotic microalgae is a green eukaryotic microalgae.

6. The composition according to claim 1 , wherein the eukaryotic microalgae is of the Chlorophyta, preferably Chlorella.

7. 2. The composition of claim 1, wherein the eukaryotic microalgae is selected from one or more of Chlorella autotrophica, Chlorella colonials, Chlorella lewinii, Chlorella minutissima, Chlorella pituta, Chlorella pulchelloides, Chlorella pyrenoidosa, Chlorella rotunda, Chlorella singularis, Chlorella sorokiniana, Chlorella variabilis, Chlorella volutis, and Chlorella vulgaris.

8. 10. The composition of claim 1, wherein the extract may comprise one or more of proteins, lipids, vitamins, minerals, folic acid, iron, fiber, and / or pigments.

9. 9. The composition of claim 8, wherein the protein is selected from one or more of plastocyanin (A0A2P6TGD1), glycine-rich 2 (A0A2P6TDY2), SMAD FHA domain containing (A0A2P6U3K7), chloroplast thylakoid lumen kDa (A0A2P6TNZ5), peptidyl prolyl isomerase (A0A2P6TGB0), calmodulin (A0A2P6TFR8), 10 kDa chaperonin-like (A0A2P6THP7), membrane isoform A (A0A2P6TEF6), L-induced nipper (A0A2P6TU12), beta-Ig-H3 fasciclin (A0A2P6TQQ9).

10. The composition of any one of claims 1 to 9, wherein the composition is administered topically.

11. A compound derivable from eukaryotic microalgae for use in the treatment of viral diseases.

12. A composition comprising a eukaryotic microalga or an extract thereof for use as an inhibitor of the binding of the spike protein receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2).

13. The composition of claim 12, which does not affect ACE2 activity.

14. Use of eukaryotic microalgae or extracts thereof as antiviral agents.

15. A composition comprising a prokaryotic microalgae or an extract thereof for use in said treatment of a viral disease.

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