Peptides with antiviral activity

Abstract

The invention relates to organic chemistry, pharmacology and medicine and concerns novel antiviral peptides. The claimed peptides are characterized by a high level of antiviral activity and show promise for use in the treatment of infectious diseases caused by a viral infection, inter alia, diseases caused by SARS-CoV-2 such as, for example, a simple infection (such as a fever, a cough and / or a sore throat), pneumonia, acute or severe respiratory infection, hypoxic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock and, in particular, COVID-19.

Description

[0001] Peptides with antiviral activity

[0002] Field of technology

[0003] The invention relates to the chemistry of organic compounds, pharmacology and medicine and concerns new peptides characterized by antiviral activity, which, in particular, can be used for the prevention and treatment of viral diseases in a subject.

[0004] State of the art

[0005] Infectious diseases, particularly those caused by viruses, are a major cause of morbidity and mortality in humans. They account for a large share of deaths and disabilities worldwide. The recent outbreak of coronavirus disease 2019 (COVID-19) illustrates the burden of viral diseases and disorders. COVID-19 is an infectious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Common symptoms of COVID-19 include fever, cough, and shortness of breath. Despite intensive countermeasures implemented worldwide, morbidity and mortality remain high, and many countries are facing new waves of infection. Vaccines are an important tool in the fight against COVID-19, but the development of antiviral drugs is also a priority, particularly with the emergence of variants that may partially evade vaccines.

[0006] Known antiviral drugs have proven ineffective in combating the novel coronavirus pandemic. Therefore, a safe and effective treatment for the prevention and treatment of the novel coronavirus is urgently needed in clinical practice. Given that existing antiviral drugs have varying degrees of shortcomings, developing antiviral drugs with improved therapeutic efficacy is an urgent challenge. The development of direct-acting antiviral agents is crucial. In this regard, peptides are increasingly being developed as therapeutic agents for the treatment of many diseases.

[0007] The prior art discloses the use of dalargin hexapeptide in the production of medicinal products intended for the treatment of COVID-19 coronavirus infection (RU2728939).

[0008] The prior art also discloses new peptides that can block the binding interaction of the novel coronavirus SARS-CoV-2 in mammals, in particular by inhibiting the interaction between the coronavirus spike protein and the ACE2 receptor (US2024218020, US11667678, EP4333867).

[0009] Thus, attempts to create new peptide molecules with pharmacological activity seem appropriate and relevant. Disclosure of the invention

[0010] The objective of the present invention is to develop and create new effective antiviral agents that are promising for use in clinical practice for the treatment and / or prevention of infectious diseases, in particular diseases caused by SARS-CoV-2, for example, a simple infection (such as fever, cough and / or sore throat), pneumonia, acute or severe respiratory infection, hypoxic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock, in particular COVID-19.

[0011] The technical result of the invention is the development and production of new peptide compounds that have an infectious effect and are promising for use in the treatment of antiviral diseases, in particular, diseases caused by SARS-CoV-2, for example, a simple infection (such as fever, cough and / or sore throat), pneumonia, acute or severe respiratory infection, hypoxic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock, in particular COVID-19.

[0012] The stated technical result is achieved through the development and creation of a peptide with antiviral activity, having the sequence SEQ ID NO: 1, 2, or 3, or a pharmaceutically acceptable salt thereof. More specifically, the peptides according to the invention are characterized by antiviral activity against coronavirus. In particular embodiments of the invention, the coronavirus is SARS-CoV-2.

[0013] The present invention also includes the use of the peptide of the invention as an antiviral agent. More specifically, the use of the peptide of the invention as an antiviral agent against coronavirus. In particular embodiments of the invention, the coronavirus is SARS-CoV-2.

[0014] The present invention also provides the use of the peptide of the invention for the production of a pharmaceutical composition with antiviral activity for the treatment and / or prevention of an infectious disease in a subject. More specifically, a pharmaceutical composition with antiviral activity against coronavirus. In certain embodiments, the coronavirus is SARS-CoV-2.

[0015] The present invention also provides a pharmaceutical composition with antiviral activity for the treatment and / or prevention of an infectious disease in a subject, comprising an effective amount of a peptide of the invention or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient. More specifically, the pharmaceutical composition has antiviral activity against coronavirus. In certain embodiments of the invention, the coronavirus is SARS-CoV-2.

[0016] In particular embodiments of the invention, the disease is a disease caused by SARS-CoV-2, such as a simple infection (such as fever, cough and / or sore throat), pneumonia, acute or severe respiratory infection, hypoxemic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock, in particular COVID-19.

[0017] In particular embodiments of the invention, the pharmaceutically acceptable excipient is a carrier, filler and / or solvent.

[0018] In particular embodiments of the invention, the subject is a human being.

[0019] The present invention also includes the preparation of compounds (peptides) according to the invention.

[0020] The present invention also includes a method for treating and / or preventing an infectious disease in a subject by administering to the subject a peptide of the invention or a pharmaceutical composition of the invention. In particular embodiments of the invention, the disease is a disease caused by a coronavirus, including SARS-CoV-2, for example, a simple infection (such as fever, cough, and / or sore throat), pneumonia, acute or severe respiratory infection, hypoxemic respiratory failure, acute respiratory distress syndrome, sepsis, or septic shock, in particular COVID-19.

[0021] The present invention also includes a method for blocking and / or inhibiting a coronavirus, such as the SARS-CoV-2 virus, including the Delta B.1.617.2 variant or the Omicron BA.4 / 5 variant, using the peptide of the invention or the pharmaceutical compositions of the invention.

[0022] Detailed disclosure of the invention

[0023] Brief description of the drawings

[0024] Figure 1. Reduction in the infectious titer of the SARS-CoV-2 virus (strain SV-534, variant Delta B.1.617.2) under the action of the peptides according to the invention in a therapeutic model regimen.

[0025] Figure 2. Reduction in the infectious titer of the SARS-CoV-2 virus (strain SV-657, variant Omicron BA.4 / 5) under the action of the peptides according to the invention in a therapeutic model regimen. Definitions and terms

[0026] For a better understanding of the present invention, certain terms used in this description of the invention are provided below. The following definitions apply throughout this document unless otherwise specified.

[0027] In the description of this invention, the terms "includes" and "comprising" are interpreted to mean "includes, among other things." These terms are not intended to be construed as meaning "consists solely of."

[0028] The term "and / or" means one, more than one, or all of the listed elements.

[0029] Also here, listing numeric ranges by endpoints includes all numbers within that range.

[0030] The term "optional" or "optional" or "optionally" as used herein means that the subsequently described event or circumstance may, but does not necessarily, occur, and that the description includes instances in which the event or circumstance occurs and instances in which it does not occur.

[0031] The term "amino acid" also refers to naturally occurring amino acids (including both L-amino acids and D-amino acids). Amino acids are designated by standard abbreviations: arginine (Arg; R), leucine (Leu; L), lysine (Lys; K), phenylalanine (Phe; F), tryptophan (Trp; W), isoleucine (He; I), tyrosine (Tyr; Y).

[0032] The compounds that form the essence of this invention may exist in radioisotope-labeled form, i.e., said compounds may contain one or more atoms whose atomic mass or mass number differs from the atomic mass or mass number of the most common natural isotopes. Radioisotopes of hydrogen, carbon, phosphorus, and chlorine include 3 H, 14 WITH, 32 R, 35 S, and 36 C1, respectively. Compounds of the present invention that contain such radioisotopes and / or other radioisotopes of other atoms are within the scope of the present invention. Tritiated, i.e. 3 H and carbon, i.e. 14 Radioisotopes are particularly preferred due to their ease of preparation and detection.

[0033] The radiolabeled compounds of the present invention can be prepared using methods well known to those skilled in the art. Labeled compounds can be prepared using the procedures described herein by simply replacing unlabeled reagents with the appropriate labeled reagents.

[0034] The compounds of the present invention may exist in free form or, if desired, as a pharmaceutically acceptable salt or other derivative. The term "pharmaceutically acceptable salt" as used herein refers to those salts that, within the scope of medical judgment, are suitable for use in contact with human and animal tissues without undue toxicity, irritation, allergic reaction, etc., and that meet a reasonable benefit-risk ratio. Pharmaceutically acceptable salts of amines, carboxylic acids, phosphonates, and other types of compounds are well known in the medical field. Salts can be prepared in situ during the isolation or purification of the compounds of the invention, and can also be prepared separately by reacting the free acid or free base of the compound of the invention with a suitable base or acid, respectively.Examples of pharmaceutically acceptable, non-toxic acid salts include salts of the amino group formed with inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric and perchloric acids, or organic acids such as acetic, oxalic, maleic, tartaric, succinic or malonic acids, or obtained by other methods used in the art, such as ion exchange.Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanate, hydroiodide, 2-hydroxyethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, Picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valeriate, and the like. Typical alkali and alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and others.In addition, pharmaceutically acceptable salts may contain, if desired, non-toxic ammonium, quaternary ammonium and amine cations prepared using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates and aryl sulfonates.

[0035] A "therapeutically effective amount" is defined as the amount of a compound administered or delivered to a patient that is most likely to produce the desired response to treatment for infectious diseases caused by a viral infection, particularly coronavirus. The exact amount required may vary from subject to subject depending on the patient's age, body weight, and general condition, the severity of the disease, the method of administration, whether the patient is being treated with other drugs, etc.

[0036] A "prophylactically effective amount" is defined as the amount of a compound administered or delivered to a patient that is most likely to produce the desired response to prevent infectious diseases caused by a viral infection, particularly coronavirus. The exact amount required may vary from subject to subject depending on the patient's age, body weight, and general condition, the method of administration, combination prophylaxis with other drugs, etc. For prophylactic treatment, a therapeutically or prophylactically effective amount is the amount that will be effective in preventing a viral infection, particularly one caused by SARS-CoV-2.

[0037] The term "patient" ("subject") encompasses all mammalian species, preferably humans, that utilize the compounds of the invention, either by self-administration and / or administration to the patient by another person, for the treatment and / or prevention of a disease or medical condition.

[0038] The terms "treatment" and "therapy" cover the treatment of pathological conditions in mammals, preferably in humans, and include: a) blocking (stopping) the course of the disease, b) alleviating the severity of the disease, i.e. inducing regression of the disease.

[0039] The terms "prophylaxis," "avoidance," and "preventive therapy" encompass the elimination of risk factors, as well as prophylactic treatment of subclinical stages of disease in humans, aimed at reducing the likelihood of developing clinical stages of the disease. Patients for prophylactic therapy are selected based on factors that, based on known data, increase the risk of developing clinical stages of the disease compared to the general population. Preventive therapy includes (a) primary prevention and (b) secondary prevention. Primary prevention is defined as prophylactic treatment in patients who have not yet reached the clinical stage of the disease. Secondary prevention is the prevention of recurrence of the same or a similar clinical state of the disease.

[0040] The term "risk reduction" encompasses therapies that reduce the incidence of clinical disease. Examples of risk reduction include primary and secondary disease prevention.

[0041] The term "antiviral agent," as used herein, refers to a compound or combination of compounds capable of: (i) inhibiting, reducing, or preventing the entry of a virus into a cell; (ii) inhibiting or reducing the ability of a virus to cause infection in a subject; or (iii) inhibiting or reducing the ability of a virus to replicate or remain infectious in the environment. The term "antiviral agent" also refers to compounds capable of reducing the infectivity or virulence of a virus.

[0042] One skilled in the art will appreciate that the peptide described herein can exist and is often used in the form of its pharmaceutically acceptable derivatives, such as salts, prodrugs, metabolites, esters, ethers, hydrates, polymorphs, solvates, complexes, enantiomers, or other pharmaceutically acceptable derivatives. Therefore, reference to a peptide described herein is intended to include such pharmaceutically acceptable salts, prodrugs, metabolites, esters, ethers, hydrates, polymorphs, solvates, complexes, enantiomers, or any other pharmaceutically acceptable derivatives thereof.

[0043] Pharmaceutical compositions

[0044] The invention also relates to pharmaceutical compositions that comprise a peptide of the invention (or a prodrug, a pharmaceutically acceptable salt or other pharmaceutically acceptable derivative) and one or more pharmaceutically acceptable carriers, adjuvants, solvents and / or excipients, such that can be administered to a patient together with the compound that is the essence of this invention and that do not destroy the pharmacological activity of this compound and are non-toxic when administered in doses sufficient to deliver a therapeutic amount of the compound.

[0045] The pharmaceutical compositions referred to in this invention comprise the peptides of the present invention together with pharmaceutically acceptable carriers, which may include any solvents (in particular water), diluents, dispersions or suspensions, surfactants, isotonic agents, thickeners and emulsifiers, preservatives, binders, lubricants, etc., suitable for a particular dosage form.Materials that can serve as pharmaceutically acceptable carriers include, but are not limited to, mono- and oligosaccharides and derivatives thereof; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut, cottonseed, sesame, olive, corn and soybean oils and others; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; depyrogenated water; isotonic solution, Ringer's solution; alcohol and phosphate buffer solutions. The composition may also contain other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release agents, film agents, sweeteners, flavorings and aromatizers, preservatives and antioxidants.

[0046] The present invention also includes dosage forms—a class of pharmaceutical compositions whose structure is optimized for a specific route of administration at a therapeutically effective dose, such as intravenous, oral, intramuscular, subcutaneous, inhalational, intranasal, and sublingual administration at recommended dosages. The dosage forms of this invention may contain structures obtained using liposomes, microencapsulation, nanoformulations of the drug, or other methods known in the pharmaceutical arts.

[0047] For parenteral administration, aqueous suspensions, isotonic saline solutions or sterile injection solutions are used, the compatible agents of which contain pharmacological agents, for example, propylene glycol or butylene glycol.

[0048] In particular embodiments of the invention, the compositions of the invention may include a peptide of the present invention conjugated to polyethylene glycol, namely, conjugation of the N-terminus of the peptide to polyethylene glycol (hereinafter referred to as PEG) [ACS Appl. Mater. Interfaces 2020, 12, 41, 46991-47001; https: / / doi.org / 10.1021 / acsami.0c13492]. There are various variations of PEG, depending on its molecular weight.

[0049] This approach allows to reduce immunogenicity, increase solubility and half-life of protein drugs [Pasut G. Pegylation of biological molecules and potential benefits: pharmacological properties of certolizumab pegol. BioDrugs. 2014;28 Suppl 1:S15-S23. Doi:10.1007 / s40259-013-0064-z]. PEG is highly soluble in water and many organic solvents, non-toxic and non-immunogenic. PEGylation of biologically active compounds allows to increase metabolic stability by creating steric hindrances that protect the molecule from proteases, and, thus, to increase circulation time in vivo.

[0050] Methods of therapeutic use

[0051] The compounds of the present invention are antiviral agents and are therefore useful agents for the treatment and / or prevention of a viral infection in a subject, including an infection caused by SARS-CoV-2.

[0052] In another aspect, the invention also relates to methods for treating or preventing a viral infection in a subject, comprising administering to the subject an effective amount of a peptide of the invention. Subjects to be treated include dogs, cats, horses, cattle, sheep, pigs, poultry, primates (e.g., rhesus and cynomolgus macaques, monkeys, marmosets, tamarins, chimpanzees, macaques), rabbits, and rodents (rats, mice, guinea pigs, and the like). In one embodiment, the subject is a human, and the antiviral peptide of the invention can be delivered topically, intranasally, etc. The antiviral peptide can be delivered in the form of drops, spray, cream, gel, ointment, and the like.

[0053] The compound or compositions described herein can also be used for prophylactic purposes. Accordingly, the compound or composition can be administered to a subject potentially at risk of developing a viral infection. Subjects at risk of developing a viral infection include individuals exposed to a particular microorganism belonging to a pathogenic bacterial species; individuals with chronic diseases, including those with impaired immune systems; or individuals over 45 years of age.

[0054] The antiviral peptides described in this invention can be used for the treatment or prevention of infectious diseases caused by SARS-CoV-2, such as a simple infection (such as fever, cough and / or sore throat), pneumonia, acute or severe respiratory infection, hypoxic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock, in particular COVID-19.

[0055] For therapeutic use, the compounds of the invention can be administered via a pharmaceutical composition in any pharmaceutical dosage form by any route of administration. Dosage forms typically include a pharmaceutically acceptable carrier suitable for the particular dosage form selected. In particular, a compound of the invention can be administered daily for a period of time necessary to treat and / or prevent the patient's condition, including courses of therapy lasting days, months, or years. Routes of administration include, but are not limited to, intravenous, intramuscular, oral, subcutaneous, inhalation, intranasal, and sublingual. The preferred route of administration is intravenous.

[0056] The invention also relates to a pharmaceutical composition comprising a daily dose of said compound in the form of a fixed dosage unit, and to a combination comprising said pharmaceutical composition or said compound. In a preferred embodiment, said composition for use in accordance with the invention is administered once daily at a dosage of 1 mg or more of the selected compound according to the invention. The preferred dosage is 1-500 mg. The most preferred dosage is 10-200 mg.

[0057] One or more additional pharmacologically active agents may be administered in combination with the peptide of the invention. Generally, any additional single or multiple active agents other than the compounds of the invention, including, but not limited to, other antiviral drugs, may be used in any combination with the compound of the invention in a single or separate dosage form, allowing for the simultaneous or sequential therapeutic action of the active agents. Carrying out the invention

[0058] Although the invention has been described with reference to the disclosed embodiments, it will be apparent to those skilled in the art that the specific experiments described in detail are provided merely for the purpose of illustrating the present invention and should not be construed as limiting the scope of the invention in any way. It should be understood that various modifications are possible without departing from the spirit of the present invention.

[0059] Obtaining a peptide according to the invention

[0060] General methods for obtaining the peptide according to the invention

[0061] A person skilled in the art can readily synthesize the peptide of the invention. Standard methods for producing synthetic peptides are well known in the art. The peptide of the invention can be synthesized using commonly used methods such as t-BOC or FMOC protection of alpha-amino groups. Both methods involve stepwise synthesis, with one amino acid added at each step, starting from the carboxyl terminus of the peptide. The peptide of the invention can also be synthesized using solid-phase peptide synthesis methods well known in the art.

[0062] Furthermore, the peptide of the invention can be obtained not only by chemical synthesis but also by biotechnological methods: nucleotide sequences encoding the amino acid sequence of the claimed peptide can be synthesized. These nucleotide sequences can be introduced into cells (using vectors or native nucleic acids), and the cells thus transformed can be used to express the claimed peptides. These vectors and nucleotide sequences can be introduced into the human body (and other living organisms) for direct in vivo expression of the claimed peptides. These methods are also well known to those skilled in the art.

[0063] Synthesis of peptides according to the invention

[0064] The peptides of the invention were synthesized by solid-phase Fmoc synthesis using a JBMS-96-A automated synthesizer (Jianbang Pharmacy Technology Co., Ltd.). The peptides were purified (purity >93%) using reversed-phase high-performance liquid chromatography (Table 2).

[0065] The structures of the peptides of the invention are disclosed in Table 1 below.

[0066] Table 1. Examples of peptides according to the invention. HPLC of the peptides of the invention was performed on a Phenomenex Luna® 5 pm C18(2) column (4.6*250mm*5 pm), eluting with 0.1% trifluoroacetic acid in 100% water (solvent A) and 0.1% trifluoroacetic acid in 100% acetonitrile (solvent B), at a flow rate of 1 ml / min.

[0067] Table 2. HPLC and mass spectroscopy data for the peptides of the invention.

[0068] The claimed peptides can be incorporated into other large molecules (proteins, peptides, nucleic acids, carbohydrates, lipids, conjugates) without altering their pharmacological activity or to impart new properties. Furthermore, derivatives of the claimed peptides can be obtained by chemical modification of the terminal amino acid regions.

[0069] Characteristics of biological activity

[0070] Study of the antiviral activity of peptides in an experimental in vitro model

[0071] The study of the antiviral effect of the peptides according to the invention was carried out using a continuous cell culture of Vero 102 and two strains of the SARS-CoV-2 virus СВ-534 (variant Delta B.1.617.2) and СВ-657 (variant Omicron ВА.4 / 5).

[0072] Vero 102 cells were seeded in 96-well plates at a seeding concentration of 1.2 x 10 4per well. A three-day-old cell monolayer was infected with virus-containing fluid; the calculated viral dose (MOI) was 0.01 TKI50 / cell (SARS-CoV-2 virus strains CB-534 and CB-657 were used). Two hours after inoculating the cell cultures with virus-containing fluid (model treatment regimen), peptide solutions according to the invention were added to the wells of the plate; the final peptide concentration in the wells of the plate was 10 μg / ml and 100 μg / ml (each peptide dilution was tested in duplicate). The viability of the virus was tested by infecting control wells of the plate (K+) (2 wells of the plate were infected for each virus strain), the cytopathic effect of the peptides (at a concentration of 10 μg / ml and 100 μg / ml) was assessed by adding the preparations to control wells (KO) (2 wells of the plate for each dilution of the peptides), the viability of the Vero 102 cell monolayer was assessed in control wells (K-).

[0073] Control wells (C+) were filled with virus-containing fluid only (MOI = 0.01 TCO50 / cell). Control wells (CW) were filled with peptide solutions only (at a concentration of 100 μg / ml). Control wells (C-) were filled with support medium (to an equivalent volume).

[0074] After adding the drugs and setting up controls, the cells were cultured for 4 days at 37°C in a CO2 atmosphere. On day 4, the appearance of cytopathic effect (CPE) was noted in control wells (K+). On day 4 (after the cytopathic effect was detected), aliquots were taken from the wells and frozen at -70°C for subsequent determination of the concentration of live viral particles and viral RNA.

[0075] The concentration of viable viral particles was determined by titration using the TCD / 50 method on a continuous Vero 102 cell culture; the virus concentration was calculated using the Spearman-Kaerber method. The concentration of SARS-CoV-2 viral RNA was determined by real-time PCR. Viral RNA was isolated using the commercial RiboPrep reagent kit (Central Research Institute of Epidemiology, Rospotrebnadzor, Russia) according to the manufacturer's instructions. Amplification with real-time hybridization-fluorescence detection was performed using the AmpliSens® SARS-CoV-2-IT test system (Central Research Institute of Epidemiology, Rospotrebnadzor, Russia) in accordance with the manufacturer's instructions on a CFX96 plate-type amplification system (Bio-Rad, USA). To determine the amount of SARS-CoV-2 viral RNA, standard samples with a known concentration of viral RNA (in genome equivalents per 1 ml of supernatant sample (genome equivalent / ml)) were used.

[0076] A comparative analysis of the decrease in the infectious titer of viruses under the influence of peptides was performed compared to the control (K+). The decrease in infectious titer was expressed in units (AlgTCID50). The coefficient of inhibition of the cytopathic effect of the virus (CI) was also determined as a percentage using the standard formula CI = [(Ak - Ao) / Ac] x 100, where Ac is the level of virus accumulation during cultivation without the addition of the studied agent to the nutrient medium (lg TCID50 / ml) and Ao is the level of virus accumulation during cultivation with the addition of the studied agent to the nutrient medium (lg TCID50 / ml).

[0077] The obtained results of the study are presented in Figures 1-2.

[0078] The peptides according to the invention (including BAT102, BAT94, BAT2) at a concentration of 100 μg / ml had an antiviral effect against the SARS-CoV-2 virus strain СВ-534, variant Delta B.1.617.2, leading to a decrease in the titer of viable viral particles by 1.33-1.41 lg and a decrease in the concentration of viral RNA, the inhibition coefficient was 30.12-31.92%.

[0079] The peptides of the invention (including BAT 102) at a concentration of 100 μg / ml exhibited antiviral activity against the SARS-CoV-2 virus strain CB-657, variant Omicron BA.4 / 5, resulting in a 1.35 lg decrease in the titer of viable viral particles and a 30.34% decrease in the viral RNA concentration. Although the invention has been described with reference to the disclosed embodiments, it will be apparent to those skilled in the art that the specific experiments described in detail are provided for illustrative purposes only and should not be construed as limiting the scope of the invention in any way. It will be appreciated that various modifications are possible without departing from the spirit of the invention.

Claims

Invention formula 1. A peptide with antiviral activity, or a pharmaceutically acceptable salt thereof, having a sequence selected from the sequence SEQ ID N0: 1, 2, 3.

2. Use of the peptide according to paragraph 1 as an antiviral agent.

3. A pharmaceutical composition with antiviral activity for the treatment and / or prevention of an infectious disease in a subject caused by a viral infection, containing an effective amount of the peptide according to claim 1 or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable excipient.

4. The pharmaceutical composition according to claim 3, characterized in that the pharmaceutically acceptable excipient is a carrier, filler and / or solvent. / 5. The pharmaceutical composition according to claim 3, characterized in that the disease is caused by a coronavirus.

6. The pharmaceutical composition according to claim 5, characterized in that the coronavirus is SARS-CoV-2.

7. The pharmaceutical composition according to claim 5, wherein the disease is COVID-19.

8. The pharmaceutical composition according to claim 5, wherein the disease is a simple infection such as fever, cough and / or sore throat, pneumonia, acute or severe respiratory infection, hypoxic respiratory failure, acute respiratory distress syndrome, sepsis or septic shock.

9. A pharmaceutical composition according to paragraph 3, in which the subject is a human being.

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