ES2953479A1 - Use of sIFNAR2 in the treatment of SARS-CoV-2 infection (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

Use of the soluble receptor sIFNAR2 in the treatment of SARS-CoV-2 coronavirus infection and compositions comprising said protein. (Machine-translation by Google Translate, not legally binding)

Description

DESCRIPTION

Use of sIFNAR2 in the treatment of SARS-CoV-2 infection

FIELD OF THE INVENTION

The present invention is within the field of biomedicine and biotechnology, and refers to the use of the recombinant soluble receptor sIFNAR2 in the treatment of infection by the SARS-CoV-2 coronavirus.

BACKGROUND OF THE INVENTION

The advances made in the therapy of viral diseases are of lesser magnitude than those that have been achieved for the treatment of bacterial infections. The development of highly effective broad-spectrum antiviral agents is a primary goal shared by the fields of virology and pharmacology.

Viruses are intracellular parasites that use the metabolic machinery of the infected host cell. Therefore, the development of antivirals presents a series of difficulties associated with this obligate parasitic character. It is difficult to achieve adequate antiviral activity without affecting the metabolism of the host cell and without causing negative effects on other uninfected cells in the body.

Current strategies to control viral infectivity are based on the identification of agents capable of intervening in the essential steps of viral infection, such as entry (fusion, endocytosis), replication, assembly, as well as drugs directed against the viral envelope. . Another strategy would be aimed at modulating the cellular defense system.

The identification of broad-spectrum antiviral agents focused on reducing viral infectivity or modulating host defenses would make an important contribution to the field of virology for the improvement of human health and control of viral epidemics.

In the 21st century, we have seen coronaviruses emerge in Asia, the East and the West. Coronaviruses are a family of viruses that cause respiratory diseases. In 2002-2003, severe acute respiratory syndrome (SARS) affected 238 people and killed 33 in Singapore, including healthcare workers. Ten years after that, the Middle East respiratory syndrome coronavirus (MERS or nCoV-2012) emerged in the Middle East and continues to emerge with sporadic cases and localized outbreaks, including one in Korea. The outbreak of pneumonia caused by the acute respiratory disease Novel Coronavirus 2019-nCoV (also named as COVID-19 by WHO on February 11, 2020) in Wuhan, Hubei Province of China, at the end of 2019 is a great challenge for public health and clinical treatment. All of these coronaviruses have had significant human morbidity and mortality. These RNA viruses with crown-shaped spikes on their envelope have been predicted to be emerging pathogens with outbreak potential due to their inherent propensity for rapid mutation and recombination due to their large genomes.

Currently, it is urgent to investigate antiviral drugs that could be useful in the treatment of COVID-19 caused by the SARS-CoV2 coronavirus.

The use of interferons is key in the search for these antiviral treatments.

Type I interferons (alpha, beta and omega) exert their action through the interaction with the membrane receptor IFNAR, formed by two subunits IFNAR1 and IFNAR2.

Specifically, in the case of interferon beta - IFNB, after the binding of IFNB to IFNAR2, the dimerization of the two subunits occurs and the activation of the intracellular signaling cascade whose signal is transduced to the nucleus through the Jak-pathway. Stat. In this way, the antiviral, antiproliferative and immunomodulatory activities of IFNB are exerted.

The IFNAR2 subunit of the receptor undergoes alternative processing of the mRNA that gives rise to three different isoforms: a short isoform (IFNAR2b), a long functionally active isoform (IFNAR2c) and the soluble isoform (sIFNAR2, IFNAR2.3 or IFNAR2a).

Only IFNAR2c acts as a functional receptor together with IFNAR1 and is capable of mediating the biological effects of IFNB.

sIFNAR2, which lacks cytoplasmic and transmembrane domains, has been identified in human biological fluids and although its role is not defined, it has been suggested that it may have neutralizing capacity for the binding of IFNB to the IFNAR2 receptor. Thus It could exert modulating functions depending on the concentration at which it is found; On the one hand, it could neutralize the binding of IFNB to the IFNAR receptor or, on the contrary, prolong the half-life of circulating IFNB, preventing its degradation or the formation of oligomers. To date, the function of the soluble variant of IFNAR2 remains unknown.

In studies carried out with transgenic mice that after infection with SARS-CoV-2 develop a pathology similar to that of seriously ill patients or those suffering from persistent COVID (Sefik, E. et al., 2021), the use of antibodies against IFNAR2 that inhibit its signal in combination therapy to treat persistent COVID, as an improvement was observed in these mice and a reduction in their inflammatory state.

Other authors (Hurtado-Guerrero, J. et al, 2020) point out that the biological activity of sIFNAR2 is very similar to that of interferon beta-IFN-p, also producing a decrease in pro-inflammatory cytokines, showing an antiproliferative effect and presenting a antiviral activity against the encephalomyocarditis virus.

Other studies confirmed that the administration of sIFNAR2 in in vivo treatment in murine models with multiple sclerosis produced an improvement in the severity of the disease, a reduction in the activation state of CD4+ T lymphocytes and a greater decrease in the inflammatory process than the other two types of treatment under study, proposing its use in the treatment of diseases that cause inflammation (Suardíaz, M. et al., 2016).

Thus, both Hurtado-Guerrero, J. et al. like Suardíaz, M. et al. point out that the in vitro and in vivo activity of IFNAR2.3 could be very similar to that of interferon beta-IFN-p. In both cases this activity appears to be independent of the presence of IFN-p and appears to occur through the activation of a different cellular signaling pathway.

In contrast, other studies (Samarajiwa, S. A. et al., 2014) indicate that the immunomodulatory activity of sIFNAR2 seems to derive from a greater activation of the IFN-p signaling pathway, at least in the response produced in septic shock.

Thus, the specific function of the soluble variant of IFNAR2 and the mechanism of action that mediates its biological activity are not yet clear.

In WO2017/109257, the antiviral activity of the soluble isoform of sIFNAR2 is demonstrated against some single-stranded RNA viruses such as encephalomyocarditis, vesicular stomatitis, human immunodeficiency virus, human respiratory syncytial virus and metapneumovirus. human.

However, none of the previous studies suggest the application of the soluble isoform of sIFNAR2 in the treatment of infections caused by viruses of the Coronaviridae family, such as SARS-CoV-2. The influence that sIFNAR2 could have on the evolution of an infection with SARS-CoV-2 is also not addressed in the state of the art.

The inventors of the present invention have verified the antiviral effect of a recombinant protein sIFNAR2, analogous to the soluble isoform of the IFNB receptor, against SARS-Cov2.

DESCRIPTION OF THE INVENTION

The authors of the present invention have produced the sIFNAR2 protein recombinantly, a protein analogous to the human soluble IFN beta receptor: It was cloned in E.coli and has 239 amino acids and a molecular weight of 29 KDa. This protein has been tested in the Coronavirus unit of the National Center for Microbiology in cellular models infected with Coronavirus.

Vero cells were infected with SARS-Cov-2 (MOI: 0.001) for 48 hours in the presence of 5 different concentrations of sIFNAR2 (3.75, 7.5, 10, 30 and 60 (ug/ml). With the concentration of 60ug/ml A significant reduction in the number of PFU/ml was found.

Subsequently, under the same conditions, it was observed how viral growth decreased as the concentration of sIFNAR2 increased.

Cell viability was not affected at any of the sIFNAR2 concentrations tested.

Uses of the protein of the invention

Therefore, a first aspect of the invention refers to the use of a protein with an identity of at least:

a) 90% with SEQ ID NO: 2,

b) 95% with SEQ ID NO: 2,

c) 99% with SEQ ID NO:2,

or a protein of amino acid sequence SEQ ID NO: 2, hereinafter “protein of the invention”, for the prevention, improvement, alleviation and/or treatment of coronavirus infection.

Coronaviruses are organisms of the Virus Superkingdom, order Nidovirales, suborder Cornidovirineae Family Coronaviridae ; Subfamily Orthocoronavirinae ; Genus Betacoronavirus ; Subgenus Sarbecovirus; Severe acute respiratory syndrome related coronavirus species.

In a preferred embodiment of the invention the coronavirus SARS-CoV-2.

Furthermore, the use of antibodies or fragments thereof capable of binding to the recombinant protein of the invention are also an object of the present invention. These antibodies or fragments thereof can be easily obtained from antisera.

Antisera to the recombinant protein described in the present invention can be generated by standard techniques, for example, by injection of the protein of the invention into an appropriate animal and collecting and purifying the antisera from the animals. Antibodies or fragments thereof that bind to SEQ ID NO: 2, or a variant sequence thereof according to the invention can be identified by standard immunoassays. The antibodies thus obtained (hereinafter referred to as antibodies of the invention) can be used for the diagnostic method of the invention. Preferably, the antibodies or fragments thereof are monoclonal antibodies.

Thus, in another aspect the invention relates to an antibody or a fragment thereof that specifically recognizes the protein of the invention, hereinafter antibody of the invention, for use as a medicine for the prevention, improvement, relief and/or or treatment and/or relief of coronavirus infection. It also refers to the use of the antibody of the invention for the diagnosis of a coronavirus infection. Antibodies contemplated in the context of the present invention include polyclonal antisera, purified IgG molecules, supernatants or ascitic fluid containing monoclonal antibodies, Fv, Fab, Fab' and F(ab') ₂ fragments, ScFvdiabodies, triabodies, tetrabodies and humanized antibodies.

Composition of the invention

Another aspect of the invention relates to a composition, hereinafter "composition of the invention", comprising the protein of the invention or the antibody of the invention, for the prevention, improvement, alleviation and/or treatment of infection. by coronavirus.

In a preferred embodiment of this aspect of the invention, the composition is a pharmaceutical composition that optionally further comprises a pharmaceutically acceptable carrier and/or pharmaceutically acceptable excipients.

In another preferred embodiment of this aspect of the invention, the composition of the invention further comprises another active ingredient. Preferably, this active ingredient is selected from the list consisting of other antivirals, analgesics, antipyretics, decongestants or other active ingredients used in the treatment of viral diseases.

In another preferred embodiment of this aspect of the invention, the coronavirus is SARS-CoV2

"Adjuvants" and "pharmaceutically acceptable vehicles" refer to those substances, or combinations of substances, known in the pharmaceutical sector, used in the preparation of pharmaceutical forms of administration and include, but are not limited to, solids, liquids, solvents or surfactants. . The pharmaceutically acceptable carriers that can be used in the present invention are those carriers known in the state of the art.

The dosage to obtain a therapeutically effective amount depends on a variety of factors, such as the age, weight, sex or tolerance, of the individual to whom it is administered. In the sense used in this description, the expression "therapeutically effective amount" refers to the amount of the pharmaceutical composition of the invention that produces the desired effect and, in general, will be determined, among other causes, by the characteristics of said compounds and said pharmaceutical composition and the therapeutic effect to be achieved.

In a preferred embodiment of this aspect of the invention, the composition of the invention comprises another active ingredient. Preferably, the active ingredient is selected from the list consisting of other antivirals, analgesics, antipyretics, decongestants or other active ingredients used in the treatment of viral diseases.

In another preferred embodiment, the composition of the invention further comprises a pharmaceutically acceptable carrier. In another preferred embodiment, the composition of the invention further comprises another active ingredient or therapeutic agent. Said therapeutic agent is preferably selected from an analgesic agent (in the treatment of inflammation and pain) or an anti-infective agent (in the prevention of infection).

In particular, non-limiting examples of useful therapeutic agents according to the invention include the following therapeutic categories: analgesics, such as non-steroidal anti-inflammatory drugs, opiate agonists and salicylates; anti-infective agents, such as anthelmintics, antianaerobics, antibiotics, aminoglycoside antibiotics, antifungal antibiotics, cephalosporins, macrolide antibiotics, various beta-lactam antibiotics, penicillins, quinolone antibiotics, sulfonamide antibiotics, tetracycline antibiotics, antimycobacterial, antituberculous antimycobacterial, antiprotozoal, antiprotozoal antimalarials, antiviral agents, antiretroviral agents, scabicides, anti-inflammatory agents, anti-inflammatory corticosteroids, antipruritic/local anesthetics, anti-infectives, anti-infective topical antifungals, anti-infective topical antivirals, electrolytic and renal agents, such as acidifying agents, alkalinizing agents, diuretics, inhibitors of carbonic anhydrase, diuretics, loop diuretics, osmotic diuretics, potassium-sparing diuretics, thiazide diuretics, electrolyte supplements, and uricosuric agents, enzymes, such as pancreatic enzymes and thrombolytic enzymes, gastrointestinal agents, such as antidiarrheals, antiemetics gastrointestinal, gastrointestinal anti-inflammatory agents, salicylate anti-inflammatory agents, antacids anti-gastric ulcer, acid pump inhibitory agents anti-ulcer agents, gastric mucosa anti-ulcer agents H ₂ blocking agents, anti-ulcer agents, cholelitholytic agents, digestive agents, emetics, laxatives and stool softeners and prokinetic agents, general anesthetics such as halogenated inhalation anesthetics inhalation anesthetics, intravenous anesthetics, barbiturates, benzodiazepines intravenous anesthetics intravenous anesthetics opiates and intravenous anesthetics agonists, hormones and hormone modifiers, such as abortifacients, adrenal corticosteroid agents, adrenal agents, androgens, antiandrogens, immunobiological agents, such as immunoglobulins, immunosuppressants, toxoids, and vaccines; local anesthetics, such as amide local anesthetics and ester-type local anesthetics, musculoskeletal agents, such as anti-gout anti-inflammatory agents, corticosteroids anti-inflammatory agents, gold compounds anti-inflammatory immunosuppressive agents, anti-inflammatory agents, drugs non-steroidal anti-inflammatory drugs (NSAIDs), salicylate anti-inflammatory agents, minerals and vitamins, such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E and vitamin K.

In a particular embodiment, useful therapeutic agents according to the above categories include: (1) general analgesics, such as lidocaine or its derivatives, and analgesic non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, ibuprofen, ketoprofen, naproxen and, ( 2) opiate agonist analgesics, such as codeine, fentanyl, hydromorphone and morphine, (3) salicylate analgesics, such as aspirin (ASA), (4) antihistamine H1 blockers, such as terfenadine, clemastine and (5) anti-infective agents , such as mupirocin; (6) anti-anaerobic anti-infectives, such as chloramphenicol and clindamycin; (7) antifungal anti-infective antibiotics, such as amphotericin B, clotrimazole, fluconazole and ketoconazole; (8) against macrolide -infectious antibiotic, such as azithromycin and erythromycin; (9) various beta-lactam anti-infectives, such as aztreonam and imipenem; (10) anti-infective penicillin antibiotic, such as nafcillin, oxacillin, penicillin G, penicillin V and; (11) quinolone anti-infective antibiotics, such as ciprofloxacin and norfloxacin; (12) anti-infective tetracycline antibiotic, such as doxycycline, minocycline and tetracycline; (13) anti-infective anti-tuberculosis anti-mycobacterial drugs, such as isoniazid (INH), rifampicin and; (14) anti-infective antiprotozoals, such as atovaquone and dapsone; (15) anti-infectious anti-protozoal antimalarials, such as chloroquine and pyrimethamine; (16) anti-retroviral anti-infectives, such as ritonavir and zidovudine; (17) against antiviral-infectious agents, such as acyclovir, ganciclovir, interferon alfa, and rimantadine; (18) topical anti-infective antifungals, such as amphotericin B, clotrimazole, miconazole, nystatin and; (19) topical anti-infective antivirals, such as acyclovir; (20) electrolyte and renal agents, such as lactulose; (21) loop diuretics, such as furosemide, (22) potassium-sparing diuretics, such as triamterene; (23) thiazide diuretics, such as hydrochlorothiazide (HCTZ), (24) uricosuric agents, such as probenecid; (25) enzymes, such as RNase and DNase; (26) antiemetics, such as prochlorperazine; (27) salicylate gastrointestinal anti-inflammatory agents, such as sulfasalazine; (28) Gastric acid pump anti-ulcer inhibitor agents, such as omeprazole; (29) H ₂ blockers, anti-ulcer agents, such as cimetidine, famotidine, nizatidine and ranitidine; (30) digestive, such as pancrelipase; (31) prokinetic agents, such as erythromycin (32; ester); local anesthetics, such as benzocaine and procaine; (33) musculoskeletal corticosteroid anti-inflammatory agents, such as beclomethasone, betamethasone, cortisone, dexamethasone, hydrocortisone, and prednisone; (34) musculoskeletal anti-inflammatory immunosuppressants, such as azathioprine, cyclophosphamide and methotrexate; (35) musculoskeletal non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ibuprofen, ketoprofen, ketorlac, and naproxen; (36) minerals, such as iron, calcium and magnesium; (37) Vitamin B compounds, such as cyanocobalamin (vitamin B12) and niacin (vitamin B3); (38) vitamin C compounds, such as ascorbic acid, and (39) vitamin D compounds, such as calcitriol.

As used herein, the term "active ingredient", "active substance", "pharmaceutically active substance", "active ingredient" or "pharmaceutically active ingredient" means any component that potentially provides a pharmacological activity or other different effect in the diagnosis, cure, mitigation, treatment, or prevention of a disease, or that affects the structure or function of the body of man or other animals. The term includes those components that promote a chemical change in the preparation of the drug and are present in the drug in an intended modified form that provides the specific activity or effect.

The term "medicine", as used herein, refers to any substance used for prevention, diagnosis, alleviation, treatment or cure of diseases or prevention of unwanted physiological states in man and animals.

The term "individual", as used in the description, refers to animals, preferably mammals, and more preferably, humans. The term “individual” is not intended to be limiting in any aspect, and may be of any age, sex and physical condition.

The amino acid sequence of sIFNAR2 is found with accession number in GenBank (NCBI) L41943.1, here named as SEQ ID NO: 2.

In the context of the present invention, sIFNAR2 is also defined by a nucleotide or polynucleotide sequence, which constitutes the coding sequence of the protein included in SEQ ID NO: 2, and which would comprise various variants from:

a) nucleic acid molecules that encode a polypeptide comprising the amino acid sequence of SEQ ID NO: 2,

b) nucleic acid molecules whose complementary chain hybridizes with the polynucleotide sequence of a),

c) nucleic acid molecules whose sequence differs from a) and/or b) due to the degeneration of the genetic code,

d) nucleic acid molecules that encode a polypeptide comprising the amino acid sequence with an identity of at least 90%, 95%, 98% or 99% with SEQ ID NO: 2, and in which the polypeptide encoded by said nucleic acids, it has the activity and structural characteristics of the sIFNAR2 protein.

Among these nucleic acid molecules is the one contained in the GenBank (NCBI) sequence L41943.1, here named as SEQ ID NO: 1.

The terms “polynucleotide” and “nucleic acid” are used interchangeably here, referring to polymeric forms of nucleotides of any length, both ribonucleotides (RNA or RNA) and deoxyribonucleotides (DNA or DNA).

The terms "amino acid sequence", "peptide", "oligopeptide", "polypeptide" and "protein" are used interchangeably herein, and refer to a polymeric form of amino acids of any length, which may be coding or non-coding, chemically or biochemically modified.

Throughout the description and claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and features of the invention will emerge partly from the description and partly from the practice of the invention. The The following examples and drawings are provided by way of illustration, and are not intended to be limiting of the present invention.

DESCRIPTION OF THE FIGURES

Fig. 1 . Evaluation of sIFNAR2 in Vero E6 cells infected with SARS-Cov-2. The cells were infected with SARS-Cov-2 (MOI: 0.001) for 48 hours in the presence of 5 different concentrations of sIFNAR2 (3.75, 7.5, 10, 30 and 60 (ug/ml). With the concentration of 60ug/ml A significant reduction in the number of PFU/ml was found.

Fig. 2. Evaluation of sIFNAR2 in Vero E6 cells infected with SARS-Cov-2. The cells were infected with SARS-Cov-2 (MOI: 0.001) for 48 hours in the presence of 5 different concentrations of sIFNAR2 (3.75, 7.5, 10, 30 and 60 (ug/ml). It was observed how viral growth decreased. as the concentration of sIFNAR2 increases.

Fig. 3 . Evaluation of cell viability in the presence of sIFNAR2. Vero E6 cells were exposed for 72 hours in the presence of 5 different concentrations of sIFNAR2 (3.75, 7.5, 10, 30 and 60 (ug/ml) and subsequently the percentage of cell viability was evaluated by the MTT method. The viability was close to 100% in all concentrations tested.

EXAMPLES OF THE INVENTION

Material and methods

The cloning of the protein was carried out at the IBIMA Research Laboratory (Málaga, Spain) The experiments with SARS-CoV2 were carried out at the "National Center for Microbiology. Carlos NI Health Institute" (Madrid, Spain ).

Ethics and safety

The different experiments were carried out with the safety protocols and facilities required at each center, including Biosafety Levels (BSL) 2 to 3 as necessary.

Statistics

In these studies, sample sizes were not required and exclusively descriptive statistics (n and percentages) were used.

Cloning and purification of rh-sIFNAR2

The protein cloning and purification process is briefly described. The prokaryotic expression system pEcoli-Cterm 6xHN Linear (Clontech®) was chosen to ligate the sIFNAR2 insert and after that, the DH5a Competent Cells™ (Invitrogen®) were transformed with the plasmid. The purified plasmid was introduced into BL21 (DE3) bacteria (Invitrogen®) to produce recombinant sIFNAR2. After purification, recombinant sIFNAR2 was detected by Western blot using anti-IFNAR2 human MaxPab antibody (Abnova®) and identified by mass spectrometry (MALDI-TOF) (Supplementary Figure 1: Identification of the protein by Western blot and by mass spectrometry).

After that, each batch of soluble 6xHN-tagged sIFNAR2 protein was purified by affinity chromatography on an ÁKTA FPLC system (GE Healthcare), according to standard procedures. Fractions were analyzed on 10% SDS polyacrylamide gels stained with Coomassie Brilliant Blue (BIORAD). Recombinant sIFNAR2 protein was dialyzed against phosphate-buffered saline (PBS) and then quantified and loaded onto a gel. The final product has a purity greater than 95%. Protein densitometry was performed using ImageJ 1.440 software (HIH, Bethesda, MD) to determine their concentration.

Endotoxin levels were determined using the Endosafe®-PTS™ system and “Limulus Amebocyte Lysate” (LAL) kinetic chromogenic test cartridges with a sensitivity of 0.005 EU mL-1 (Charles River Laboratories). Endotoxin levels in the dilutions The working values used for all experiments were less than 1 EU mL-1, which is equivalent to an amount of endotoxin less than 0.1 ng mL-129-31.

Antiviral activity against SARS-CoV-2 infection in Vero E6 cells

To study the antiviral capacity of the rh-sIFNAR2 compound, M24 wells were infected in triplicate with confluent Vero E6 cells at a multiplicity of infection (MOI) of 0.001 with rSARS-CoV-2-WT (Wuhan Hu-1 GenBank MN908947), in the presence of different concentrations of rh-sIFNAR2 compound (60-3.75 ^g/ml). The infection was incubated for 48 hours and the supernatant was subsequently taken for assessment by plaque lysis assay.

It was observed that viral growth decreased as the concentration of sIFNAR2 increased (Fig. 2) and that at a concentration of 60ug/ml there was a significant reduction in the number of PFU/ml (Fig. 1).

On the other hand, an MTT test was carried out to study the toxicity of this compound in Vero E6 cells, testing different concentrations ranging from 60 to 3.75 ^g / ml, incubated for 72 hours, without altering the viability in any of the tested concentrations. Viability was close to 100% at all concentrations tested.

References

1. Sefik, E. et al 2021, "Viral replication in human macrophages enhances an inflammatory cascade and interferon driven chronic COVID-19 in humanized mice", bioRxiv 2021.09.27.461948. https://doi.org/10.1101/2021.09.27.461948 .

2. Hurtado-Guerrero, J. et al, 2020, "Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-B Mediation", Jounal of Clinical Medicine, 9, 959; doi:10.3390/jcm9040959.

3. Suardíaz, M. et al., 2016, "Recombinant soluble IFN receptor (sIFNAR2) exhibits intrinsic therapeutic efficacy in a murine model of Multiple Sclerosis", Neuropharmacology Volume 110, Part A, Pages 480-492.

4. Samarajiwa, SA et al., 2014, “Soluble IFN Receptor Potentiates In Vivo Type I IFN Signaling and Exacerbates TLR4-Mediated Septic Shock” J Immunol, 192 (9) 4425 4435; DOI: https://doi.org/ 10.4049/jimmunol.1302388

Claims (5)

1. A protein with an identity of at least: a) 90% with SEQ ID NO: 2, or b) 95% with SEQ ID NO: 2, or c) 99% with SEQ ID NO: 2; either or a protein of amino acid sequence SEQ ID NO: 2, for use in the treatment of SARS-CoV-2 infection. 2- A composition comprising the protein according to claim 1, for use in the treatment of SARS-CoV-2 infection 3.- The composition according to the previous claim, which is a pharmaceutical composition. 4.- The composition according to any of claims 2-3, which further comprises a pharmaceutically acceptable vehicle and/or pharmaceutically acceptable excipients. 5.- The composition according to any of claims 2-4, which also comprises another active ingredient.