Promising Directions for the Development of Chemotherapy for Viral Infections
https://doi.org/10.37489/0235-2990-2025-70-3-4-69-83
EDN: ROVYIR
Abstract
Viral infections occupy a leading place in various human pathologies and are one of the main causes of death among people, both in developed and developing countries with a weak health care system. The huge diversity of viruses and their unique variability pose a serious challenge to the developers of antiviral agents. The purpose of this review is to analyze the current state of development of emergency prevention and treatment agents, as well as promising areas for the development of chemotherapy for viral infections. The main direction in the development of effective means for the treatment of viral infections is the creation of medications based on abnormal nucleosides and their precursors, small interfering RNA, releaseactive compounds, and the search for targets among viral proteins. The review considers the most significant results in the field of creating agents for the treatment of viral infections.
Keywords
viral infections,
abnormal nucleosides,
release-active substances,
broad-spectrum drugs,
RNA interference
Supporting agencies: The authors declare no conflict of interest.
About the Authors
S. Ya. Loginova
48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Svetlana Ya. Loginova — D. Sc. in Biology, Leading Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Sergiev Posad
Competing Interests:
The authors declare no conflict of interest.
S. V. Borisevich
48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Sergey V. Borisevich — D. Sc. in Biology, Professor, Academician of the Russian Academy of Sciences, Head of the 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Sergiev Posad
Competing Interests:
The authors declare no conflict of interest.
V. N. Shсhukina
48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Veronika N. Shchukina — Ph. D. in Biology, Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Sergiev Posad
Competing Interests:
The authors declare no conflict of interest.
S. V. Savenko
48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Sergey V. Savenko — Senior Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Sergiev Posad
Competing Interests:
The authors declare no conflict of interest.
V. V. Rubtsov
48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Vladimir V. Rubtsov — Ph. D. Veterinary Sciences, Researcher, 48th Central Scientific Research Institute of the Ministry of Defense of the Russian Federation
Sergiev Posad
Competing Interests:
The authors declare no conflict of interest.
References
1. Mühlemann B., Vinner L., Margaryan A. et al. Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking AgeЮ Science. 2020; 369 (6502): eaaw 8977. doi: 10.1126/science.aaw8977.
2. Basler C. F. Influenza viruses: Basic biology and potential drug targets. Infect Disord Drug Targets. 2007; 7: 282–293. doi: 10.2174/187152607783018745.
3. Furuyama W., Marzi A. Ebola virus: pathogenesis and countermeasure development. Annu Rev Virol. 2019; 6: 435–458. doi: 10.1146/annurevvirology-092818-015708.
4. Dyall J., Gross R., Kindrachuk J. et al. Middle East respiratory syndrome and severe acute respiratory syndrome: Current therapeutic options and potential targets for novel therapies. Drugs. 2017; 77: 1935–1966. doi: 10.1007/s40265-017-0830-1.
5. Millet J. K., Whittaker G. R. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015; 202: 120–134. doi: 10.1016/j.virusres.2014.11.021.
6. Ling R., Dai Y., Huang B., Huang W., Yu J., Lu X., Jiang Y. In silico design of antiviral peptides targeting the spike protein of SARS-CoV-2. Peptides. 2020; 130: 170328. doi: 10.1016/j.peptides.2020.170328.
7. WHO Coronavirus (COVID-19) dashboard. 2023. https://covid19.who.int/?mapFilter=cases).
8. Galegov G. A. Etiotropnaya lekarstvennaya terapiya virusnykh infektsij. Voprosy Virusologii. 2004; 3: 35–40. (in Russian)
9. Bovin N. V. Novye podkhody k pro-tivovirusnoj terapii. Molekulyarnaya Meditsina. 2004;. 3: 56–61. (in Russian)
10. Izbrannye materialy Rossijskoj zaochnoj elektronnoj nauchno-prakticheskoj konferentsii «Sozdanie i klinicheskie ispytaniya lekarstvennykh sredstv. Sovremennaya farmakoterapiya virusnykh infektsij» (7–12 noyabrya 2005 goda, g. Volgograd). Lekarstvennyj vestnik. 2006; 3 (5): 37–54. (in Russian)]
11. Goncalves B. C., Barbosa M. G. L., Olak A. P. S. et al. Antiviral therapies: Advances and perspectives. Fundam Clin Pharmacol. 2021; 35: 305–320. doi: 10.1111/fcp.12609.
12. De Clercq E., Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016; 29: 695–747. doi: 10.1128/CMR.00102-15.
13. Hughes D., Andersson D. I. Evolutionary consequences of drug resistance: Shared principles across diverse targets and organisms. Nat Rev Genet. 2015; 16: 459–471. doi: 10.1038/nrg3922.
14. Cele S., Jackson L., Khoury V. et al. Omicron extensively but incompletely escapes Pfizer B. N.T162b2 neutralization. Nature. 2022; 602: 654–656. doi: 10.1038/s41586-021-04387-1.
15. Outlaw V. K., Bovier F. T., Mears M. C. et al. Inhibition of Coronavirus Entry in vitro and ex vivo by a lipid-conjugated peptide derived from the SARS-CoV-2 spike glycoprotein HRC domain. mBio. 2020; 11: e01935–20. doi: 10.1128/mBio.01935-20.
16. de Vries R. D., Schmitz K. S., Bovier F. T. et al. Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science. 2021; 371: 1379–1382. doi: 10.1126/science.abf4896.
17. Luteijn R. D., Praest P., Thiele F. et al. A broad-spectrum antiviral peptide blocks infection of viruses by binding to phosphatidylserine in the viral envelope. Cells. 2020; 9: 1989. doi: 10.3390/cells9091989.
18. Brice D. C., Diamond G. Antiviral Activities of Human Host Defense Peptides. Curr Med Chem. 2020; 27: 1420–1443. doi: 10.2174/0929867326666190805151654.
19. Kim M. I., Pham T. K., Kim D. et al. Identification of brevinin-1EMaderived stapled peptides as broad-spectrum virus entry blockers. Virology. 2021; 561: 6–16. doi: 10.1016/j.virol.2021.05.004.
20. Zhao H., Zhou J., Zhang K. et al. A novel peptide with potent and broadspectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016; 6: 22008. doi: 10.1038/srep22008.
21. Sample C. J., Hudak K. E., Barefoot B. E. et al. A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses. Peptides. 2013; 48: 96–105. doi: 10.1016/j.peptides.2013.07.014.
22. Li Q., Zhao Z., Zhou D. et al. Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses. Peptides. 2011; 32: 1518–1525. doi: 10.1016/j.peptides.2011.05.015.
23. Lu S., Pan X., Chen D. et al. Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses. Bioorg Chem. 2021; 107: 104619. doi: 10.1016/j.bioorg.2020.104619.
24. ElSawy K.M., Twarock R., Verma C. S., Caves L. S. Peptide inhibitors of viral assembly: A novel route to broad-spectrum antivirals. J Chem Inf Model. 2012; 52: 770–776. doi: 10.1021/ci200467s.
25. Zannella C., Mosca F., Mariani F. et al. Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense. Mar Drugs. 2017; 15: 182. doi: 10.3390/md15060182.
26. Pessi A., Bixler S. L., Soloveva V. et al. Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo. Antivir Res. 2019; 171: 104592. doi: 10.1016/j.antiviral.2019.104592.
27. Benedict A., Bansal N., Senina S. et al. Repurposing F. D.A-approved drugs as therapeutics to treat Rift Valley fever virus infection. Front Microbiol. 2015; 6: 676. doi: 10.3389/fmicb.2015.00676.
28. Descamps V., Helle F., CLouandre C. et al. The kinase-inhibitor sorafenib inhibits multiple steps of the Hepatitis C Virus infectious cycle in vitro. Antiviral Res. 2015; 118: 93–102. doi: 10.1016/j.antiviral.2015.03.012.
29. Gao M., Duan H., Liu J. et al. The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins. Antiviral Res. 2014; 106: 80–5. doi: 10.1016/j.antiviral.2014.03.009.
30. Michaelis M., Paulus C., N. Loschmann N. et al. The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication. Cell Mol Life Sci. 2011; 68 (6): 1079–90. doi: 10.1007/s00018-010-0510-8.
31. Randhawa P. S., Farasati N. A., Y. Huang Y. et al. Viral drug sensitivity testing using quantitative PCR: effect of tyrosine kinase inhibitors on polyomavirus BK replication. Am J Clin Pathol. 2010; 134 (6): 916–20. doi: 10.1309/AJCP7JYHJN1PGQVC.
32. Roberts J. L., Tavallai M., A. Nourbakhsh A. et al. GRP78/Dna K Is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. J Cell Physiol. 2015; 230 (10): 2552–78. doi: 10.1002/jcp.25014.
33. Brahms A., Mudhasani R., Pinkham C. et al. Sorafenib impedes rift valley fever virus egress by inhibiting valosin-containing protein function in the cellular secretory pathway. J Virol. 2017; 91 (21): e00968–17. doi: 10.1128/jvi.00968-17.
34. De Angelis M., Casciaro B., Genovese A. et al. Temporin G., an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: insights into biological activity and mechanism of action. FASEB J. 2021; 35: e21358. doi: 10.1096/fj.202001885RR.
35. Loginova S. A., Borisevich S. V., Maksimov V. A., Bondarev V. P., Kotovskaya S. K., Rusinov V. L., Charushkin V. N., Chupakhin O. N. Therapeutic efficacy of triazavirin, a novel russian chemotherapeutic, against influenza virus A (H5N1). Antibiot Khimioter = Antibiotics and Chemotherapy. 2011; 56 (1-2): 10–12. (in Russian)]
36. Loginova S.Ya., Borisevich S. V., Rusinov V. L., Ulomsky E. N., Charushin V. N., Chupakhin O. N., Sorokin P. V. Investigation of therapeutic efficacy of triazavirin against experimental forest-spring encephalitis on albino mice. Antibiot Khimioter = Antibiotics and Chemotherapy. 2015; 60 (7-8): 11–13. (in Russian)
37. Loginova S. Ya., Borisevich S. V., Rusinov V. L., Ulomsky 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 = Antibiotics and Chemotherapy. 2015; 60 (5-6): 8. (in Russian)
38. Kok W. M. New developments in flavivirus drug discovery. Expert Opin Drug Discov. 2016; 11 (5): 433–45. doi: 10.1517/17460441.2016.1160887.
39. De Clercq E. Antiviral agents: characteristic activity spectrum depending on the molecular target with which they interact. Adv Virus Res. 1993; 42: 1–55. doi: 10.1016/s0065-3527(08)60082-2.
40. Loginova S. Ya., Borisevich S. V., Maksimov V. A., Bondarev V. P., Nebolsin V. E.Therapeutic efficacy of Ingavirin®, a new russian formulation against influenza a virus (H3N2). Antibiot Khimioter = Antibiotics and Chemotherapy. 2008; 53 (7–8): 27–30. (in Russian)
41. Loginova S.Ya., Borisevich S. V., Lykov M. V., Vedenina E. V., Borisevich G. V., Bondarev V. P., Nebolsin V. E., Chuchalin A. G. In vitro efficacy of ingavirin against the mexican pandemic subtype H1N1 of influenza A virus, strains A/California/04/2009 and A/California/07/2009. Antibiot Khimioter = Antibiotics and Chemotherapy. 2009; 54 (3–4): 15–17. (in Russian)
42. Poordad F., McCone J., Bacon B. R. et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364 (13): 1195–1206.
43. De Clercq E. Highlights in antiviral drug research: antivirals at the horizon. Med Res Rev. 2013; 33 (6): 1215–1248. doi: 10.1002/med.2125
44. Wu S. F., Lee C.-J., Liao C.-L. et al. Antiviral effects of an iminosugar derivative on flavivirus infections. J Virol. 2002; 76 (8): 3596–3604. doi: 10.1128/jvi.76.8.3596-3604.2002.
45. McCormick J. B., King L. J., Webb P. A. et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986; 314 (1): 20–26. doi: 10.1056/NEJM198601023140104.
46. Khaggins D., Syan ChyuB Krosgriff T. i dr. Perspektivnoe, dvazhdy shifrovannoe, odnovremennoe, platsebo-kontroliruemoe klinicheskoe isledovanie vnutrivennoj terapii ribavirinom gemorragicheskoj likhoradki s pochechnym sindromom (GLPS). Mezhdunarodnyj simppozium po GLPS, 5–10 maya, 1991, Leningrad. 1991; 15. (in Russian)
47. Huggins J. W., Hsiang C. M., Cosgriff T. M. Chemotherapy of HFRS. 1-st Int. Conf. HFRS, may 4–6, 1989, Seoul, Korea — Seoul, 1989; 84.
48. Watts D. M., Ussery M. A., Nash D., Peters C. J. Inhibition of CrimeanCongo hemorrahagic fever viral infectivity yields in vitro by ribavirin. Am J Trop Med Hyg. 1989; 41 (5): 581–585. doi: 10.4269/ajtmh.1989.41.581.
49. Sterhen E. L., Jones D. E., Peters C. J. et al. Ribavirn treatment of toga-, arena- and bunyaviruses infection in subhuman primates and other animal species. In: Ribavirin broad spectrum agent. R. A. Smith (ed.). Acad. Press, 1980; 4: 170–174.
50. Delang L., Guerrero N. S., Tas A. et al. Mutations in the chikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broadspectrum antiviral. J Antimicrob Chemother. 2014; 69 (10): 2770–2784. doi: 10.1093/jac/dku209.
51. Bassetto M., de Burghgraeve T., Delang L. et al. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antiviral Res. 2013; 98 (1): 12–18. doi: 10.1016/j.antiviral.2013.01.002.
52. Parashar D., Cherian S. Antiviral perspectives for chikungunya virus. Biomed Res Int. 2014; 631642. doi: 10.1155/2014/631642.
53. Kim J. A., Seong R. K., Kumar M., Shin O. S. Favipiravir and ribavirin inhibit replication of Asian and African strains of Zika Virus in different cell models. Viruses. 2018; 10 (2): E72. doi: 10.3390/v10020072.
54. Cai L., Sun Y., Song Y. et al. Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication. Arch Virol. 2017; 162 (9): 2847–2853. doi: 10.1007/s00705-017-3436-8.
55. Julander J. G., Shafer K., Smee D. F. et al. Activity of T-705 in a hamster model of yellow fever virus infection in comparison with that of a chemically related compound, T-1106. Antimicrob Agents Chemother. 2009; 53 (1): 202–209. doi: 10.1128/AAC.01074-08.
56. Morrey J. D., Smee D. F., Sidwell R. W., Tseng C. K. Identification of active compounds against a New York isolate of West Nile virus. Antiviral Research. 2002; 55: 107–116. doi: 10.1016/s0166-3542(02)00013-x.
57. Gowen B. B., Wong M. H., Jung K. H. et al. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob. Agents Chemother. 2007; 51: 3168–3176. doi: 10.1128/AAC.00356-07.
58. Oestereich L., Rieger T., Lüdtke A. et al. Efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of Lassa fever. J Infect Dis. 2016; 213: 934–938. doi: 10.1093/infdis/jiv522.
59. Westover J. B., Sefing E. J., Bailey K. W. et al. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses. Antiviral Res. 2016; 126: 62–68. doi: 10.1016/j.antiviral.2015.12.006.
60. Rosenke K., Feldmann H., Westover J. B. et al. Use of favipiravir to treat lassa virus infection in macaques. Emerg Infect Dis. 2018; 24 (9): 1696–1699. doi: 10.3201/eid2409.180233.
61. Oestereich L., Ludtke A., Wurr S. et al. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014; 105: 17–21. doi: 10.1016/j.antiviral.2014.02.014.
62. Smither S. J., Eastaugh L. S., Steward J. A. et al. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014; 104: 153–155. doi: 10.1016/j.antiviral.2014.01.012.
63. Bai C. Q., Mu J.S., Kargbo D., Song Y. B. et al. Clinical and virological characteristics of ebola virus disease patients treated with favipiravir (T-705)- Sierra Leone, 2014. Clin Infect Dis. 2016; 63 (10): 1288–1294. doi: 10.1093/cid/ciw571.
64. Sissoko D., Laouenan C., Folkesson E. et al. Experimental treatment with favipiravir for ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016; 13 (3): e1001967. doi: 10.1371/journal.pmed.1001967.
65. Schibler M., Vetter P., Cherpillod P. et al. Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report. Lancet Infect Dis. 2015; 15 (9): 1034–1040. doi: 10.1016/S1473-3099(15)00229-7.
66. Mora-Rillo M., Arsuaga M., Ramirez-Olivencia G. et al. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med. 2015; 3 (7): 554–562. doi: 10.1016/S2213-2600 (15)00180-0.
67. Zhu W., Zhang Z., He S. et al. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral Res. 2018 Mar; 151: 39–49. doi: 10.1016/j.antiviral.2018.01.011.
68. Dawes B. E., Kalveram B., Ikegami T. et al. Favipiravir (T-705) protects against Nipah virus infection in the hamster model. Sci Rep. 2018; 8 (1): 7604. doi: 10.1038/s41598-018-25780-3.
69. Morrey J. D., Taro B. S., Siddharthan V. et al. Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents. Antiviral Res. 2008; 80 (3): 377–379. doi: 10.1016/j.antiviral.2008.07.009.
70. Qiu L., Patterson S. E., Bonnac L. F., Geraghty R. J. Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis. PLoS Negl Trop Dis. 2018; 12 4): e0006421. doi: 10.1371/journal.pntd.0006421.
71. Caroline A. L., Powell D. S., Bethel L. M. et al. Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever. PLoS Negl Trop Dis. 2014; 8 (4): 2790. doi: 10.1371/journal.pntd.0002790.
72. Julander J. G., Smee D. F., Morrey J. D., Furuta Y. Effect of T-705 treatment on western equine encephalitis in a mouse model. Antiviral Res. 2009; 82 (3): 169–171. doi: 10.1016/j.antiviral.2009.02.201.
73. Marathe B. M., Wong S.-S., Vogel P. et al. Combinations of oseltamivir and t-705 extend the treatment window for highly pathogenic influenza A (H5N1) virus infection in mice. Sci Rep. 2016; 6: 26742. doi: 10.1038/srep26742.
74. Boyd J. E., Sommerville R. G. The antiviral activity of some related benzo (b)thiophene derivatives. II. Antiinfluenza activity. Arch Ges Virusforsch. 1974; 46 (1–2): 78–85. doi: 10.1007/BF01240207.
75. Sobolevsky A. I., Koshelev S. G., Khodorov B. I. Molecular size and hydrophobicity as factors which determine the efficacy of the blocking action of amino-adamantane derivatives on NMDA channels. Membr Cell Biol. 1999; 13 (1): 79–93.
76. Griffin S. D., Harvey R., Clarke D. S. et al. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol. 2004; 85 (Pt 2): 451–461. doi: 10.1099/vir.0.19634-0.
77. Griffin S. D.C., Beales L. P., Clarcke D. S. et al. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, amantadine. FEBS Lett. 2003; 535: 34–38. doi: 10.1016/s0014-5793(02)03851-6.
78. Kelly M. L., Cook J. A., Brown-Augsburger P. et al. Demonstrating the intrinsic ion channel activity of virally encoded proteins. FEBS Lett. 2003; 552: 61–67. doi: 10.1016/s0014-5793(03)00851-2.
79. Tanner J. A., Zheng B. J., Zhou J. et al. The Adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus. Chem Biol. 2005; 12 (3): 303–311. doi: 10.1016/j.chembiol.2005.01.006.
80. Timofeyev D. I., Perminova N. G., Kiseleva Ya. Yu., Nekludov V. V., Vatolin G. Yu., Grebinik T. S., Timofeyev I. V., Serbin A. V., Kasyan L. I. HIV-inhibiting activity of polyanionic matrixes and based on them substances containing adamantane and norbornene pharmacophores. Antibiot Khimioter = Antibiotics and Chemotherapy. 2003; 48 (5): 33–41. (in Russian)
81. Serbin A. V., Alikhanova O. L., Timofeev I. V. i dr. Rol' membranotropnykh alitsiklicheskikh farmakoforov v terapevticheskoj zashchite ot virusa immunodefitsita cheloveka (VICh). Perspektivy razvitiya khimii i prakticheskogo primeneniya alitsiklicheskikh soedinenij. Tezisy dokladov mezhdunarodnoj nauchno-tekhnicheskoj konferentsiiyu Samara, 2004; 37–38. (in Russian)
82. Burstein M. E., Serbin A.V., Khakhulina T. V. et al. Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents. Antiviral Res. 1999; 41 (3): 135–44.
83. Serbin A. V., Klimochkin Yu. N., Stotskaya L. L. i dr. Alitsiklicheskie ingibitory zhiznennogo tsikla virusov. 1. Adamantansoderzhashchie polianionnye sistemy. Tezisy dokladov mezhdunarodnoj nauchno-tekhnicheskoj konferentsii «Perspektivy razvitiya khimii i prakticheskogo primeneniya alitsiklicheskikh soedinenij». Samara, 2004; 225. (in Russian)
84. Kozeletskaya K. L., Stotskaya L. L., Serbin A. V. i dr. Struktura i protivovirusnaya aktivnost' adamantansoderzhashchikh polimernykh preparatov. Voprosy virusologii. 2003; 48 (5): 19–26. (in Russian)
85. Rybalko S., Nesterova N., Diadiun S. et al. Therapeutical effect of modified adamantane copolymer compounds: study of molecular mechanisms. Acta Biochim Pol. 2001; 48 (1): 241–249.
86. Horvat S., Varga-Defterdarovic L., Horvat J. et al. Synthesis and bioactivity studies of 1-adamantanamine derivatives of peptides. J Pept Sci. 1995; 1 (5): 303–310. doi: 10.1002/psc.310010505.
87. Vamecq J., Van derpoorten K., Poupaert J. H. et al. Anticonvulsant phenytoinergic pharmacophores and anti-HIV activity — preliminary evidence for the dual requirement of the 4-aminophthalimide platform and the N- (1-adamantyl) substitution for antiviral properties. Life Sci. 1998; 63 (19): 267–274. doi: 10.1016/s0024-3205(98)00445-7.
88. Barrientos L. G., O’Keefe B. R., Bray M. et al. Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res. 2003; 58: 47–56. doi: 10.1016/s0166-3542(02)00183-3.
89. Shchelkunov S. N. Molekulyarnye faktory virulentnosti ortopoksvirusov. Vestnik RAMN. 1998; 3: 24–29. (in Russian)
90. Matthew A. N., Leidner F., Lockbaum G. J. et al. Drug design strategies to avoid resistance in direct-acting antivirals and beyond. Chemical Reviews. 2021; 121: 3238–3270. doi: 10.1021/acs.chemrev.0c00648.
91. Adjei A. A. What is the right dose? The elusive optimal biologic dose in phase I clinical trials. J Clin Oncol. 2006; 24: 4054–4055. doi: 10.1200/JCO.2006.07.4658.
92. Fang Y., Wang J., Zhao M. et al. Progress and challenges in targeted protein degradation for neurodegenerative disease therapy. Journal of Medicinal Chemistry. 2022; 65: 11454–11477. doi: 10.1021/acs.jmedchem.2c00844.
93. Liang G., Bushman F. D. The human virome: Assembly, composition and host interactions. Nat Rev Microbiol. 2021; 19: 514–527. doi: 10.1038/s41579-021-00536-5.
94. Illescas B. M., Rojo J., Delgado R., Martin N. Multivalent glycosylated nanostructures to inhibit Ebola virus infection. J Am Chem Soc. 2017; 139: 6018–6025. doi: 10.1021/jacs.7b01683.
95. Schafer A., Xiong R., Cooper L. et al. Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry. PLoS Pathog. 2021; 17 (2): e1009312. doi: 10.1371/journal.ppat.1009312.
96. Kaptein S. J. F., Goethals O., Kiemel D. et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature. 2021; 598: 504– 509. doi: 10.1038/s41586-021-04123-9.
97. Pruijssers A. J., George A. S., Schafer A. et al. Remdesivir inhibits SARSCoV-2 in human lung cells and chimeric SARS-CoV expressing the SARSCoV-2 RNA polymerase in mice. Cell Reports. 2020; 32 (3): 107940. doi: 10.1016/j.celrep.2020.107940.
98. Pettersson M., Crews C. M. PROteolysis TArgeting Chimeras (PROTACs) — past, present and future. Drug Discov Today Technol. 2019; 31: 15–27. doi: 10.1016/j.ddtec.2019.01.002.
99. Liu X., Kalogeropulou A. F., Domingos S. et al. Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood-brain barrier penetrant PROTAC degrader of leucine-rich repeat kinase 2. J. Am. Chem. Soc. 2022; 144: 16930–16952. doi: 10.1021/jacs.2c05499.
100. Loginova S. Ya., Borisevich S. V., Maksimov V. A., Bondarev V. P., Kotovskaya S. K., Rusinov V. L., Charushin V. N. Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture. Antibiot Khimioter = Antibiotics and Chemotherapy. 2007; 52 (11–12): 18–20. (in Russian)
101. Buhrlage S. J., Bates C. A., Rowe S. P. et al. Amphipathic small molecules mimic the binding mode and function of endogenous transcription factors. ACS Chem Biol. 2009 May 15; 4 (5): 335–344. doi: 10.1021/cb900028j.
102. Qureshi A., Tantray V. G., Kirmani A. R., Ahangar A. G. A review on current status of antiviral siRNA. Rev Med Virol. 2018; 28 (4): e1976. doi: 10.1002/rmv.1976.
103. Haasnoot J., Berkhout B. RNA interference: its use as antiviral therapy. In RNA Towards Medicine. Handbook of experimental pharmacology. Berlin: Springer. 2006; 173: 117–150.
104. Haasnoot P. C., Cupac D., Berkhout B. Inhibition of virus replication by RNA interference J Biomed Sci. 2003; 10: 607–616. doi: 10.1159/000073526.
105. Hannon G. J. RNA interference. Nature. 2002; 418: 244–251. doi: 10.1038/418244a.
106. Ge Q., Filip L., Bai A. et al. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci U S A. 2004; 101: 8676–8681. doi: 10.1073/pnas.0402486101.
107. Stoppani E., Bassi I., Dotti S., Lizier M. et al. Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin. Antiviral Res. 2015; 120: 16–22. doi: 10.1016/j.antiviral.2015.04.017. Epub 2015 May 16.
108. Joshi G., Dash P. K., Agarwal A., Sharma S., Parida M. Bifunctional siRNA containing immunostimulatory motif enhances protection against pandemic H1N1 virus infection. Curr Gene Ther. 2015; 15 (5): 492–502. doi: 10.2174/1566523215666150812120547.
109. Huang D. T., Lu C-Y., Shao P. L. et al. In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery. PLoS One. 2017; 12 (4): e0174523. doi: 10.1371/journal.pone.0174523.
110. White M. D., Farmer M. I., Mirabile I. et al. Single treatment with RNAi against prion protein rescues early neuronal dysfunction and rolongs survival in mice with prion disease. PNAS. 2008; 105 (29): 10238–10243. doi: 10.1073/pnas.0802759105.
111. Geisber T., Lee A., Robbins M. et al. Postexposure protection of nonhuman primates against a lethal Ebola virus challenge with RNA interference: a proof-ofconcept study. Lancet. 2010; 375 (9729): 1896–1905. doi: 10.1016/S0140-6736(10)60357-1.
112. Seo D., Kim N. Y., Lee J. A. et al. Protection against lethal vaccinia virus infection in mice using an siRNA targeting the A5R gene. Antivir Ther. 2016; 21 (5): 397–404. doi: 10.3851/IMP3022.
113. Romantsov M. G., Galimzianov Rh. M., Lokteva O. M. et al. Experimental and clinicolaboratory evaluation of complex therapy efficacy in arboviral infections. Antibiot Khimioter = Antibiotics and Chemotherapy. 2012; 57 (7–8): 12–22. (in Russian)
114. Baer A. Protein Phosphatase-1 regulates Rift Valley fever virus replication. A. Baer, N. Shafagati, A. Benedict, et al. Antiviral Res. 2016; Vol.127: P.79–89. doi: 10.1016/j.antiviral.2016.01.007.
115. Wolf M. C., Freiberg A. N., Zhang T. et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci U S A. 2010; 107 (7): 3157–62. doi: 10.1073/pnas.0909587107.
116. Tong A., Zhang Y., Nemunaitis J. Small interfering RNA for experimental cancer therapy. J Curr Opin Mol Ther. 2005; 7 (2): 114–24.
117. Qiu S., Adema C., Lane T. A computational study of off-target effects of RNA interference. Nucleic Acids Res. 2005; 33 (6): 1834–1847. doi: 10.1093/nar/gki324.
118. Wong So C., Klein J. J., Hamilton H. L. et al. Co-Injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo. Nucleic Acid Ther. 2012; 22 (6): 380–390. doi: 10.1089/nat.2012.0389.
119. De Clercq E. Fifty Years in search of selective antiviral drugs. J Med Chem. 2019; 62: 7322–7339. doi: 10.1021/acs.jmedchem.9b00175.
120. Tompa D. R., Immanuel A., Srikanth S., Kadhirvel S. Trends and strategies to combat viral infections: a review on FDA approved antiviral drugs. Int J Biol Macromol. 2021; 172: 524–541. doi: 10.1016/j.ijbiomac.2021.01.076.
121. Chaudhuri S., Symons J. A., Deval J. Innovation and trends in the development and approval of antiviral medicines: 1987–2017 and beyond. Antivir Res. 2018; 155: 76–88. doi: 10.1016/j.antiviral.2018.05.005.
122. Ashmarin I. P., Lelekova T. V., Sanzhieva L. Ts. Ob effektivnosti ul'tramalykh doz i kontsentratsij biologicheski aktivnykh soedinenij. Izvestiya RAN. 1992; 4: 531–536. (in Russian)
123. Burlakova E. B., Konradova A. A., Mal'tseva E. L. Dejstvie sverkhmalykh doz biologicheski aktivnykh veshchestv i nizkointensivnykh fizicheskikh faktorov. Khimicheskaya Fizika. 2003; 22 (2): 390–424. (in Russian)
124. Epshtejn O. I. Regulyatornye vozmozhnosti sverkhmalykh doz. Byulleten' Eksperimental'noj Biologii i Meditsiny. 2002; Prilozhenie 4: 8–14. (in Russian)
125. Epshtejn O. I. Reliz-aktivnost' — ot fenomena do sozdaniya novykh lekarstvennykh sredstv. Byulleten' Eksperimental'noj Biologii. 2012; 154 (7): 62–67. (in Russian)
126. Epshtejn O. I. Fenomen reliz-aktivnosti i gipoteza «prostranstvennogo» gomeostaza. Uspekhi Fiziologicheskikh Nauk. 2013; 44 (3): 54–76. (in Russian).
Review
For citations:
Loginova S.Ya., Borisevich S.V., Shсhukina V.N., Savenko S.V., Rubtsov V.V. Promising Directions for the Development of Chemotherapy for Viral Infections. Antibiot Khimioter = Antibiotics and Chemotherapy. 2025;70(3-4):69-83. (In Russ.) https://doi.org/10.37489/0235-2990-2025-70-3-4-69-83. EDN: ROVYIR
Views:
18
Email this article 