JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2021, 70(1):18-25 | DOI: 10.5817/CSF2021-1-18

Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Ivan Malík1,2,*, Jozef Čižmárik1, Mária Pecháčová1, Gustáv Kováč2, Lucia Hudecová2
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic
2 Institute of Chemistry, Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Slovak Medical University in Bratislava, Slovak Republic

Since the beginning of the outbreak, a large number of clinical trials have been registered worldwide, and thousands of drugs have been investigated to face new health emergency of highly contagious COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Drug repurposing, i.e., utilizing an approved drug for a different indication, offers a time- and cost-efficient alternative for making new (relevant) therapies available to physicians and patients. Considering given strategy, many approved and investigational antiviral compounds, alone or in various relevant combinations, used in the past to fight Severe Acute Respiratory Syndrome Coronavirus-1, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus type 1, or Influenza viruses are being evaluated against the SARS-CoV-2.

Triazavirin (

TZV), a non-toxic broad--spectrum antiviral compound, is efficient against various strains of the Influenza A virus (Influenza Virus A, Orthomyxoviridae), i.e., swine flu (H1N1, or H3N2), avian influenza (H5N1, H5N2, H9N2, or highly pathogenic H7N3 strain), Influenza B virus (Influenza Virus B, Orthomyxoviridae), Respiratory Syncytial Virus (Orthopneumovirus, Pneumoviridae), Tick-Borne Encephalitis Virus (known as Forest-Spring Encephalitis Virus; Flavivirus, Flaviviridae), West Nile Virus (Flavivirus, Flavaviridae), Rift Valley Fever Virus (Phlebovirus, Bunyaviridae), and Herpes viruses (Simplexviruses, Herpesviridae) as well. In regard to COVID-19, the molecule probably reduced inflammatory reactions, thus limiting the damage to vital organs and reducing the need for therapeutic support, respectively. In addition, in silico computational methods indicated relatively satisfactory binding affinities of the

TZV ligand to both structural (E)- and (S)-proteins, non-structural 3-chymotrypsin-like protease (3-CLpro) of SARS-CoV-2 as well as human angiotensin-I converting enzyme-2 (ACE-2). The interactions between

TZV and given viral structures or the ACE-2 receptor for SARS-CoV-2 might effectively block both the entry of the pathogen into a host cell and its replication. Promising treatment patterns of COVID-19 positive patients might be also based on a suitable combination of a membrane fusion inhibitor (

umifenovir, for example) with viral RNA synthesis and replication inhibitor (

TZV).

Keywords: SARS-CoV-2; COVID-19; drug repurposing; triazavirin; Structural proteins; 3-chymotrypsin-like protease; ACE-2

Received: January 8, 2021; Accepted: February 12, 2021; Published: January 1, 2021  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Malík I, Čižmárik J, Pecháčová M, Kováč G, Hudecová L. Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Čes. slov. farm. 2021;70(1):18-25. doi: 10.5817/CSF2021-1-18.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Formi D., Cagliani R., Clerici R., Sironi M. Molecular evolution of human coronavirus genomes. Trends Microbiol. 2017; 25, 35-48, doi: 10.1016/j.tim.2016.09.001 Go to original source... Go to PubMed...
    2. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Zh., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Zh., Ma J., Liu W. J., Wang D., Xu W., Holmes E. C., Gao G. F., Wu G., Chen W., Shi W., Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395, 565-574, doi: 10.1016/S0140-6736(20)30251-8 Go to original source... Go to PubMed...
    3. Dömling A., Gao L. Chemistry and biology of SARS-CoV-2. Chem. 2020; 6, 1283-1295, doi: 10.1016/j.chempr.2020.04.023 Go to original source... Go to PubMed...
    4. Chung J. Y., Thorne M. N., Kwon Y. J. COVID-19 vaccines: The status and perspectives in delivery points of view. Adv. Drug Deliv. Rev. 2021; article in press (102 pp.), doi: 10.1016/j.arcmed.2020.12.009 Go to original source... Go to PubMed...
    5. Chen J., Wang R., Wang M., Wei G.-W. Mutations strengthened SARS-CoV-2 infectivity. J. Mol. Biol. 2020; 432, 5212-5226, doi: 10.1016/j.jmb.2020.07.009 Go to original source... Go to PubMed...
    6. Greaney A. J., Starr T. N., Gilchuk P., Zost S. J., Binshtein E., Loes A. N., Hilton S. K., Huddleston J., Eguia R., Crawford K. H. D., Dingens A. S., Nargi R. S., Sutton R. E., Suryadevara N., Rothlauf P. W., Liu Z., Whelan S. P. J., Carnahan R. H., Crowe Jr. J. E., Bloom J. D. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 2021; article in press (24 pp.), doi: 10.1016/j.chom.2020.11.007 Go to original source... Go to PubMed...
    7. Li Q., Wu J., Nie J., Zhang L., Hao H., Liu Sh., Zhao Ch., Zhang Q., Liu H., Nie L., Qin H., Wang M., Lu Q., Li X., Sun Q., Liu J., Zhang L., Li X., Huang W., Wang Y. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 2020; 182, 1284-1294, doi: 10.1016/j.cell.2020.07.012 Go to original source... Go to PubMed...
    8. Wang D., Li Z., Liu Y. An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics. J. Infect. Public Health 2020; 13, 1405-1414, doi: 10.1016/j.jiph.2020.07.004 Go to original source... Go to PubMed...
    9. Al Mamun Sohag A., Hannan M. A., Rahman S., Hossain M., Hasan M., Khan M. K., Khatun A., Dash R., Uddin M. J. Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review. Drug Dev. Res. 2021; article in press (24 pp.), doi: 10.1002/ddr.21709 Go to original source... Go to PubMed...
    10. Almasi F., Mohammadipanah F. Hypothetical targets and plausible drugs of coronavirus infection caused by SARS-CoV-2. Transbound. Emerg. Dis. 2021; article in press (15 pp.), doi: 10.1111/tbed.13734 Go to original source... Go to PubMed...
    11. Wu X., Yu K., Wang Y., Xu W., Ma H., Hou Y., Li Y., Cai B., Zhu L., Zhang M., Hu X., Gao J., Wang Y., Quin H., Wang W., Zhao M., Wu X., Zhang Y., Li L., Li K., Du Z., Mol B. W. J., Yang B. Efficacy and safety of triazavirin therapy for Coronavirus Disease 2019: A pilot randomized controlled trial. Engineering (Beijing) 2020; 6, 1185-1191, doi: 10.1016/j.eng.2020.08.011 Go to original source... Go to PubMed...
    12. Tsvetov V. M., Mirzaev K. B., Sychev D. A. Is it possible to use riamilovir to prevent infection and treat COVID-19? Klinicheskaya Praktika (In Russian) 2020; S4, 15-17, doi: 10.37489/2588-0519-2020-S4-15-17 Go to original source...
    13. Wu X., Yu K., Wang Y., Xu W., Ma H., Hou Y., Li Y., Cai B., Zhu L., Zhang M., Hu X., Gao J., Wang Y., Qin H., Zhao M., Zhang Y., Li K., Du Z., Yang B. The efficacy and safety of triazavirin for COVID-19: A trial protocol. Engineering (Beijing) 2020; 6, 1199-1204, doi: 10.1016/j.eng.2020.06.011 Go to original source... Go to PubMed...
    14. Ahamad S., Branch S., Harrelson S., Hussain M. K., Saquib M., Khan S. Primed for global coronavirus pandemic: Emerging research and clinical outcome. Eur. J. Med. Chem. 2021; 209, art. no. 112862 (23 pp.), doi: 10.1016/j.ejmech.2020.112862 Go to original source... Go to PubMed...
    15. Deyeva E. G., Rusinov V. L., Charushin V. N., Chupakhin O. N., Kiselev O. I. Antiviral preparation Triazavirin®: From screening to clinical trials. Razrabotka i Registratsiya Lekarstvennykh Sredstv. (In Russian) 2014; 2, 144-151.
    16. Tikhonova E. P., Kuzmina T. Yu., Andronova N. V., Tyushevskaya O. A., Elistratova T. A., Kuzmin A. E. Study of effectiveness of antiviral drugs (umifenovir, triazavirin) against acute respiratory viral infections. Kazan Med. J. 2018; 99, 215-223, doi: 10.17816/KMJ2018-215 Go to original source...
    17. Sologub T. V., Tokin I. I., Midikari A. S., Tsvetkov V. V. A comparative efficacy and safety of using antiviral drugs in therapy of patients with influenza. Infekssionnye Bolezni (In Russian) 2017; 15, 40-47, doi: 10.20953/1729-9225-2017-3-40-47 Go to original source...
    18. Verevshchikov V. K., Shemyakina E. K., Sabitov A. U., Batskalevich N. A. Modern etiotropic therapy of influenza and ARVI in adult patients with premorbid pathology. Antibiot. Khimioter. (Antibiotiki i khimioterapiia; In Russian) 2018; 63, 47-50.
    19. Loginova S. Ya., Borisevich S. V., Rusinov V. L., Ulomskiy U. N., Charushin V. N., Chupakhin O. N. Toxicity of triazavirin, a novel Russian antiinfluenza chemotherapeutic. Antibiot. Khimioter. (Antibiotiki i khimioterapiia; In Russian) 2012; 57, 8-10.
    20. Reshetnikova T. I. Study of the chronic toxicity of antiviral drug triazavirin. Zhurnal Veterinariya (In Russian) 2019; 8, 49-51, doi: 10.30896/0042-4846.2019.22.1.49-52 Go to original source...
    21. Cherkashchenko O. S. Influence of triazavirin on enzymes of detoxication activity. Medline.ru - Rossiyskiy Biomeditsinskiy Zhurnal (In Russian) 2011; 12, 458-463.
    22. Kasianenko K. V., Lvov N. I., Maltsev O. V., Zhdanov K. V. Nucleoside analogues for the treatment of influenza: history and experience. Zhurnal infektologii (In Russian) 2019; 11, 20-26, doi: 10.22625/2072-6732-2019-11-3-20-26 Go to original source...
    23. Chupakhin O. N., Charushin V. N., Rusinov V. L. Scientific foundations for the creation of antiviral and antibacterial preparations. Her. Russ. Acad. Sci. 2016; 86, 206-212, doi: 10.1134/S1019331616030163 Go to original source...
    24. Kiselev O. I., Deeva E. G., Melnikova T. I., Kozeletskaia K. N., Kiselev A. S., Rusinov V. L., Charushin V. N., Chupakhin O. N. A new antiviral drug triazavirin: Results of phase II clinical trial. Vopr. Virusol. (Voprosy virulogii; In Russian) 2012; 57, 9-12.
    25. Loginova S. Ya., Borisevich S. V., Maksimov V. A., Bondarev V. P., Kotovskaia S. K., Rusinov V. L., Charushin V. N., Chupakhin O. N. Therapeutic efficacy of triazavirin, a novel Russian chemotherapeutic, against Influenza Virus A (H5N1). Antibiot. Khimioter. (Antibiotiki i khimioterapiia; In Russian) 2011; 56, 10-12.
    26. Loginova S. Ya., Borisevich S. V., Rusinov V. L., Ulomskiy U. N., Charushin V. N., Chupakhin O. N. Investigation of triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture. Antibiot. Khimioter. (Antibiotiki i khimioterapiia; In Russian) 2014; 59, 3-5.
    27. Loginova S. Ya., Borisevich S. V., Rusinov V. L., Ulomskiy U. N., Charushin V. N., Chupakhin O. N., Sorokin P. V. Investigation of prophylactic efficacy of triazavirin against experimental forest-spring encephalitis on albino mice. Antibiot. Khimioter. (Antibiotiki i khimioterapiia; In Russian) 2015; 60, 8-11.
    28. Vanevskaia E. A., Mandra J. V., Khonina T. G. The clinical study of efficiency of modern antiviral drugs for the topical treatment of Herpes simplex patients. Problemy stomatologii (In Russian) 2015; 11, 4-7, doi: 10.18481/2077-7566-2015-11-4-7 Go to original source...
    29. Voinkov E. K., Drokin R. A., Ulomskiy E. N., Slepukhin P. A., Rusinov V. L., Chupakhin O. N. Crystal structure of medicinal product triazavirin. J. Chem. Crystallogr. 2019; 49, 213-218, doi: 10.1007/s10870-018-0750-2 Go to original source...
    30. Li J., Zheng S., Chen B., Butte A. J., Swamidass J. S., Lu Z. A survey of current trends in computational drug repositioning. Brief. Bioinform. 2016; 17, 2-12, doi: 10.1093/bib/bbv020 Go to original source... Go to PubMed...
    31. Xue H., Li J., Xie H., Wang Y. Review of drug repositioning approaches and resources. Int. J. Biol. Sci. 2018; 14, 1232-1244, doi: 10.7150/ijbs.24612 Go to original source... Go to PubMed...
    32. Yang Z.-W., Zhao Y.-Z., Zang Y.-J., Wang H., Zhu X., Meng J.-J., Yuan X.-H., Zhang L., Zhang Sh.-L. Rapid structure-based screening informs potential agents for coronavirus disease (COVID-19) outbreak. Chin. Phys. Lett. 2020; 37, art. no. 058701 (10 pp.), doi: 10.1088/0256-307X/37/5/058701 Go to original source... Go to PubMed...
    33. Wu Q., Zhang Y., Lü H., Wang J., He X., Liu Y., Ye Ch., Lin W., Hu J., Ji J., Xu J., Ye J., Hu Y., Chen W., Li S., Wang Ju., Wang Ji., Bi Sh., Yang H. The E protein is a multifunctional membrane protein of SARS-CoV. Genomics Proteomics Bioinformatics 2003; 1, 131-144, doi: 10.1016/s1672-0229(03)01017-9 Go to original source... Go to PubMed...
    34. Mukherjee S., Bhattacharyya D., Bhunia A. Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain. Biophys. Chem. 2020; 266, art. no. 106452 (13 pp.), doi: 10.1016/j.bpc.2020.106452 Go to original source... Go to PubMed...
    35. Acharya K. R., Sturrock E. D., Riordan J. F., Ehlers M. R. W. ACE revisited: a new target for structure-based drug design. Nat. Rev. Drug Discov. 2003; 2, 891-902, doi: 10.1038/nrd1227 Go to original source... Go to PubMed...
    36. Monteil V., Kwon H., Prado P., Hagelkrüys A., Wimmer R. A., Stahl M., Leopoldi A., Garreta E., Hurtado Del Pozo C., Prosper F., Romero J. P., Wirnsberger G., Zhang H., Slutsky A. S., Conder R., Montserrat N., Mirazimi A., Penninger J. M. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181, 905-913, doi: 10.1016/j.cell.2020.04.004 Go to original source... Go to PubMed...
    37. Rusinov V. L., Sapozhnikova I. M., Ulomskii E. N., Medvedeva N. R., Egorov V. V., Kiselev O. I., Deeva E. G., Vasin A. V., Chupakhin, O. N. Nucleophilic substitution of nitro group in nitrotriazolotriazines as a model of potential interaction with cysteine-containing proteins. Chem. Heterocycl. Comp. 2015; 51, 275-280, doi: 10.1007/s10593-015-1695-4 Go to original source...
    38. Chupakhin O. N., Rusinov V. L., Ulomsky E. N., Medvedeva N. R., Sapozhnikova I. M. Alkylation of 2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]1,2,4-triazine(4Н)-7-one and interaction of the products with N-nucleophiles. Butlerov. Commun. 2012; 31, 43-50.
    39. Karpenko I., Deev S., Kiselev O., Charushin V., Rusinov V., Ulomsky E., Deeva E., Yanvarev D., Ivanov A., Smirnova O., Kochetkov S., Chupakhin O., Kukhanova M. Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of Influenza A and B Virus replication. Antimicrob. Agents Chemother. 2010; 54, 2017-2022, doi: 10.1128/AAC.01186-09 Go to original source... Go to PubMed...
    40. Morse J. S., Lalonde T., Xu S., Liu W. R. Learning from the past: Possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. ChemBioChem 2020; 21, 730-738, doi: 10.1002/cbic.202000047 Go to original source... Go to PubMed...
    41. Pillaiyar T., Wendt L. L., Manickam M., Easwaran M. The recent outbreaks of human coronaviruses: A medicinal chemistry perspective. Med. Res. Rev. 2021; 41, 72-135, doi: 10.1002/med.21724 Go to original source... Go to PubMed...
    42. Warren T. K., Wells J., Panchal R. G., Stuthman K. S., Garza N. L., Van Tongeren S. A., Dong L., Retterer C. J., Eaton B. P., Pegoraro G., Honnold S., Bantia S., Kotian P., Chen X., Taubenheim B. R., Welch L. S., Minning D. M., Babu Y. S., Sheridan W. P., Bavari S. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 2014; 508, 402-405, doi: 10.1038/nature13027 Go to original source... Go to PubMed...
    43. Tchesnokov E. P., Feng J. Y., Porter D. P., Götte M. Mechanism of inhibition of Ebola Virus RNA-dependent RNA polymerase by remdesivir. Viruses 2019; 11, art. no. 326 (16 pp.), doi: 10.3390/v11040326 Go to original source... Go to PubMed...
    44. Brown A. J., Won J. J., Graham R. L., Dinnon K. H., Sims A. C., Feng J. Y., Cihlar T., Denison M. R., Baric R. S., Sheahan T. P. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019; 169, art. no. 104541 (10 pp.), doi: 10.1016/j.antiviral.2019.104541 Go to original source... Go to PubMed...
    45. Vankadari N. Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. Int. J. Antimicrob. Agents 2020; 56, art. no. 105998 (3 pp.), doi: 10.1016/j.ijantimicag.2020.105998 Go to original source... Go to PubMed...
    46. Gaisenok O. V. The use of viral RNA polymerase inhibitors in combination with a fusion inhibitor in the treatment of patients with COVID-19: hypothesis. Vopr. Virusol. (Voprosy virulogii; In Russian) 2020; 65, 167-175, doi: 10.36233/0507-4088-2020-65-3-167-175 Go to original source... Go to PubMed...
    47. Boriskin Y. S., Leneva I. A., Pécheur E.-I., Polyak S. J. Arbidol: a broad-spectrum antiviral compound that blocks viral fusion. Curr. Med. Chem. 2008; 15, 997-1005, doi: 10.2174/092986708784049658 Go to original source... Go to PubMed...
    48. Blaising J., Polyak S. J., Pécheur E.-I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res. 2014; 107, 84-94, doi: 10.1016/j.antiviral.2014.04.006 Go to original source... Go to PubMed...
    49. Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T., Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 2020; 11, art. no. 1620 (12 pp.), doi: 10.1038/s41467-020-15562-9 Go to original source... Go to PubMed...
    50. Huang D., Yu H., Wang T., Yang H., Yao R., Liang Z. Efficacy and safety of umifenovir for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J. Med. Virol. 2021; 93, 481-490, doi: 10.1002/jmv.26256 Go to original source... Go to PubMed...

    Return to the content


    Czech and Slovak Pharmacy

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.