Оболочечные вирусы — патогенетическая мишень лектинов цианобактерий

Лектины — группа углеводсвязывающих высокоспецифичных белков с широким спектром действия, участвующих в так называемой «первой линии» защиты организма. Эти уникальные биомолекулы проявляют высокую специфичность к различным моно- и олигосахаридам, в первую очередь, гликоконъюгатам вирусов и бактерий. Лектины цианобактерий эффективны против оболочечных вирусов и являются привлекательной альтернативой существующим синтетическим лекарственным препаратам. Известно практически полное отсутствие формирования резистентности у вирусов к этим соединениям. Цель обзора — анализ, обобщение и обсуждение результатов экспериментальных исследований in vivo и in vitro, иллюстрирующих механизмы действия и противовирусные эффекты лектинов, полученных из цианобактерий, в отношении наиболее опасных и социально значимых вирусов: SARS-Cov-2, ВИЧ, вирусов Эбола, гриппа и гепатита С. Кроме того, мы рассмотрим некоторые трудности, которые необходимо преодолеть для получения эффективных противовирусных препаратов в будущем.

1. Babich O., Sukhikh S., Larina V. et al. Algae: study of edible and biologically active fractions, their properties and applications. Plants. 2022; 11 (6): 780. doi:10.3390/plants11060780.

2. Barzkar N., Jahromi S.T., Poorsaheli H.B., Vianello F. Metabolites from marine microorganisms, micro, and macroalgae: immense scope for pharmacology. Mar. Drugs. 2019; 17 (8): 464. doi:10.3390/md17080464.

3. Schirrmeister B.E., Antonelli A., Bagheri H.C. The origin of multicellularity in cyanobacteria. Evol. Biol. 2011; 11: 45. doi:10.1186/1471-2148-11-45.

4. Tiwari A.K., Tiwari B.S. Cyanoterapeutics: an emerging field for future drug discovery. Applied Phicology. 2020; 1 (1): 44–57. https://doi.org/10.1080/26388081.2020.1744480.

5. Ughy B., Nagy C.I., Kos P.B. Biomedical potential of cyanobacteria and algae. Acta Biologica Szegediensis. 2015; 59: 203–224.

6. Shih P.M., Wu D., Latifi A. et al. Improving the coverage of the cyanobacterial phylum using diversity-driven genome sequencing. Proc. Natl. Acad. Sci. U.S.A. 2013; 110: 1053–1058. doi:10.1073/pnas.1217107110.

7. Uzair B., Tabassum S., Rasheed M., Rehman S.F. Exploring marine cyanobacteria for lead compounds of pharmaceutical importance. Revierw Article. Open Access. 2012; volume 2012. Article ID 179782. doi:10.1100/179782.

8. Stanier R.Y., Sistrom W.R., Hansen T.A. et al. Proposal to place the nomenclature of the Cyanobacteria (blue-green algae) under ther rules of the international code of nomenclature of bacteria. Int. J. Syst. Bacteriol. 1978; 28: 335–336.

9. Walter J.M., Coutinho F.N., Dutilh B.E. et al. Ecogenomics and taxonomy of cyanjbacteria phylum. Front Microbiol. 2017. doi:10.3389/fmicb.2017.02132.

10. Tan L.T., Phyo M.Y. Marine Cyanobacteria: a source of lead compounds and their clinically relevant molecular targets. Molecules. 2020; 25 (9): 2197. doi:10.3390/molecules25092197.

11. Jones M.R., Pinto E., Torres M.A. et al. CyanoMetDB, a comprehensive public database of secondary metabolites from cyanobacteria. Water Research. 2021; 196: 117017. doi:10.1016/j.watres.2021.117017.

12. Demay J., Bernard C., Reinhardt A., Marie B. Natural products from cyanobacteria: focus on beneficial activities. Mar. Drugs. 2019; 17 (6): 320. doi:103390/md17060320.

13. Singh R.S., Walia A.K., Singhhattar J. et al. Cyanobacterial lectins characteristics and their role as antiviral agents. Int. J. of Biological Macromolecules. 2017; 102: 475–496. doi:10.1016/j.biomac.2017.04.041.

14. Mazur-Marzec H., Ceglowska M., Konkel R. Pyrc K. Antiviral cyanometabolites-a review. Biomolecules. 2021; 11 (3): 474. doi:10.3390/biom11030474.

15. Fernandez-Romero J.A., Paglini M.G., Priano C. et al. Algal and cyanobacterial lectins and their antimicrobial properties. Mar. Drugs. 2021; 19 (12): 687. doi:10.3390/md19120687.

16. Maier I., Schiesti R.H., Kontaxis. Cyanovirin-N binds viral envelope proteins at the low-affinity carbohydrate binding site without direct virus neutralization ability. Molecules. 2021; 26 (12): 3621. doi:10.3390/molecules26123621.

17. Matei E., Basu R., Furey W. et al. Structure and glycan binding of a new cyanovirin-N homolog. J. Biol. Chem. 2016; 291 (36): 18967–18976. doi:10.1074/jbc.M116.740415.

18. Subramaniyan Vijayakumar, Menakha M. Pharmaceutical applications of cyanobacteria- a review. J. of Acute Medicine. 2015; 6 (1): 15–23. doi:10.1016/j.jacme.2015.02.004.

19. Щелканов М.Ю., Дедков В.Г., Галкина И.В., Магассуба Н’Ф., Зуманиги Н., Шипулин Г.А., Попова А.Ю., Малеев В.В. Районирование Африканской природноочаговой провинции в отношение филовирусных лихорадок. Вестник РАМН. 2017; 72 (5): 325–335. https://doi.org/10.15690/vramn804.

20. Shchelkanov M.Yu., Popova A.Yu., Dedkov V.G. et al. History of study and modern classification of coronaviruses (Nidovirales: Coronaviridae). Russian journal of Infection and Immunity. 2020 а; 10 (2): 221–246. (In Russ.). doi:10.15789/2220-7619-HOI-1412.

21. Lvov D.K., Shchelkanov M.Yu., Alkhovsky S.V. et al. Zoonotic viruses of Northern Eurasia. Taxonomy and Ecology. Academic Press, 2015. 452 p.

22. Trovato M., Sartorius R., D’Apice L. et al. Viral emerging diseases: challenges in developing vaccination strategies. Front. Immunol. 2020. doi:103389/fimmu.2020.02130.

23. Pollard A.J., Bijker E.M. A guide tovaccinology: from basic principles to new developments. Nat. Rev. Immunol. 2021; 21: 83–100. doi:10.1038/s41577-020-00479-7.

24. Reinolds D., Huesemann M. Viral inhibitors from macroalgae, microalgae, and cyanobacteria: a review of antiviral potential throughout pathogenesis. Algal Research. 2021; 57: 102331. doi:10.1016/j.algal.2021.102331.

25. Щелканов М.Ю., Попова А.Ю., Дедков В.Г. и др. История изучения и современная классификация коронавирусов (Nidovirales: Coronaviridae). Инфекция и иммунитет. 2020; 10 (2): 221–246. https://doi.org/10.15789/2220-7619-HOI-1412.

26. Shchelkanov M.Yu., Popova A.Yu., Dedkov V.G. History of study and modern classification of coronaviruses (Nidovirales: Coronaviridae). Russian journal of Infection and Immunity. 2020 а; 10 (2): 221–246 (In Russ.). doi:10.15789/2220-7619-HOI-1412.

27. Щелканов М.Ю., Цыбульский А.В., Дедков В.Г., Галкина И.В., Малеев В.В. Антимикробные пептиды как перспективные средства терапии первичных вирусных пневмоний. Инфекция и иммунитет. 2021; 11 (5): 837–852. https://doi.org/10.15789/2220-7619-APA-1595.

28. Andrew M., Jayaraman G. Marine sulfated polysaccharides as potential antiviral drug candidates to treat Corona virus disease (COVID-19). Carbohydr Res. 2021; 505: 108326. doi:10.1016/j.carres.2021.108326

29. Щелканов М.Ю., Ананьев В.Ю., Кузнецов В.В., Шуматов В.Б. Ближневосточный респираторный синдром: когда вспыхнет тлеющий очаг? Тихоокеанский медицинский журнал. 2015; 2: 94–98.

30. Щелканов М.Ю., Ананьев В.Ю., Кузнецов В.В., Шуматов В.Б. Эпидемическая вспышка Ближневосточного респираторного синдрома в Республике Корея (май-июль 2015 г.): причины, динамика, выводы. Тихоокеанский медицинский журнал. 2015; 3: 25–29.

31. Gribova V.V., Okun D.B., Shalfeeva E.A. et al. Cloud service for the differential clinical diagnostics of acute respiratory viral diseases (including those associated with highly contagious coronaviruses) with an application of methods of artificial intelligence. Yakut Medical Journal. 2020; (2): 44–47. doi:10.25789/YMJ.2020.70.13

32. Nikiforov V.V., Kolobukhina L.V., Smetanina S.V. et al. New coronavirus infection (COVID-19): etiology, epidemiology, clinic, diagnosis, treatment and prevention. Toolkit. M.: Department of Health of Moscow, 2020. 71 p.

33. Monteil V., Kwon H., Prado P. et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020; 181 (4): 905–913.e7. doi:10.1016/j.cell.2020.04.004.

34. Guide to virology. Viruses and viral infections of humans and animals / Ed.: D.K. Lvov. M.: MIA, 2013. 1200 p.

35. Barre A., Van Damme E.J.M., Simplicien M. et al. Man-specific lectins from plants, fungi, algae and cyanobacteria, as potential blockers for SARS-COV, MERS-COV and SARS-COV2 (COVID-19) coronaviruses: biomedical perspectives. Cells. 2021; 10 (7): 1619. doi:10.3390/cells10071619.

36. Hoffman M., Zhang L., Kruger N. et al. SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization. Cell Reports. doi:10.1016/j.celrep.2021.109017.

37. Naidoo D., Kar P., Roy A. et al. Structural insight into the binding of cyanovirin-N with the spike glycoprotein, Mpro and PLpro of SARS-CoV-2: protein-protein interactions, dynamics simulations and free energy calculations. Molecules. 2021; 26 (17): 5114. doi:10.3390/molecules26175114.

38. O’Keefe B.R., Giomarelli B., Barnard D.L. et al. Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffitsin against emerging viruses of the family Coronaviridae. J. Virol. 2010; 84 (5): 2511-2521. doi:10.1128/JVI.02322-09.

39. Millet J.K., Seron K., Labitt R.N. et al. Middle east respiratory syndrome coronavirus infection is inhibited by griffitsin. Antiviral Res. 2016. 133: 1–8. doi:10.1016/j.antiviral.2016.07.011.

40. Sami Neha, Rakhshan Ahmad, Fatma Tasneem et al. Exploring algae and cyanobacteria as a promising natural source of antiviral drug against SARSCoV-2. Biomedical J., 2021; 44 (1): 54–62. doi:10.1016/j.bj.2020.11.014.

41. Cai Y., Xu W., Gu X. et al. Griffitsin with a broad-spectrum antiviral activity by binding glycans in viral glycoprotein exhibits strong synergistic effect in combination with a pan-coronavirus fusion inhibitor targeting SARSCoV-2 spike S2 subunit. Virol. Sin. 2020; 35 (6): 857–860. doi:10.1007/s12250-020-00305-3.

42. Bhatt A., Arora P., Prajapati S.K. Can algal derived bioactive metabolites serve as potential therapeutics for the treatment of SARS-CoV-2 like viral infection? Front. Microbiol. 2020; 11: 596374. doi:10.3389/fmicb.2020.596374.

43. Lvov D.K., Shchelkanov M.Yu., Prilipov A.G. et al. Evolution of HPAI H5N1 virus in Natural ecosystems of Northern Eurasia (2005–2008). Avian Diseases. 2010. 54 (1): 483–495. doi:10.1637/8893-042509-Review.1

44. Щелканов М.Ю., Колобухина Л.В., Львов Д.К. Грипп: история, клиника, патогенез. Лечащий врач. 2011; 10: 33–38.

45. Львов Д.К., Прилипов А.Г., Щелканов М.Ю., Дерябин П.Г., Шилов А.А., Гребенникова Т.В., Садыкова Г.К., Ляпина О.В. Молекулярно-генетический анализ биологических свойств высокопатогенных штаммов вируса гриппа A/H5N1, изолированных от диких и домашних птиц в период эпизоотии в Западной Сибири (июль 2005 г.). Вопросы вирусологии. 2006; 51 (2): 15–19.

46. Щелканов М.Ю., Кириллов И.М., Шестопалов А.М., Литвин К.Е., Дерябин П.Г., Львов Д.К. Эволюция вируса гриппа А / H5N1 (1996–2016). Вопросы вирусологии. 2016; 61 (6): 245–256. https://doi.org/10.18821/0507-4088-2016-61-6-245-256.

47. Львов Д.К., Щелканов М.Ю., Федякина И.Т., Дерябин П.Г., Прошина Е.С., Пономаренко Р.А. Штамм вируса гриппа А/IIV-Anadyr/177-ma/2009 (H1N1) pdm09, адаптированный к тканям легких лабораторных мышей. Патент Российской Федерации № 2487936. Приоритет изобретения 02.02.2012.

48. Gulyaeva M., Sobolev I., Sharshov K., Kurskaya O. et al. Characterization of avian-like Influenza A (H4N6) virus isolated from Caspian seal in 2012. Virologica Sinica. 2018 ; 33 (5): 449–452. DOI:10.1007/s12250-018-0053-y

49. Tong S., Li Y., Rivailler P., Conrardy C. et al. A distinct lineage of influenza A virus from bats. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109 (11): 4269–4274.

50. Щелканов М.Ю., Львов Д.К. Новый субтип вируса гриппа А от летучих мышей и новые задачи эколого-вирусологического мониторинга. Вопросы вирусологии. 2012; (Приложение 1): 159–168.

51. O’Keefe B.R., Smee D.F., Turpin J. et al. Potent anti-influenza activity of cyanovirin –N and interactions with viral hemagglutinin. Antimicrob. Agents Chemother. 2003; 47 (8): 2518–2525.

52. Щелканов М.Ю., Магассуба Н., Дедков В.Г. и др. Природный резервуар филовирусов и типы связанных с ними эпидемических вспышек на территории Африки. Вестник РАМН. 2017; 72 (2): 112–119. https://doi.org/10.15690/vramn803.

53. Щелканов М.Ю., Дедков В.Г., Галкина И.В., Магассуба Н’Ф., Зуманиги Н., Шипулин Г.А., Попова А.Ю., Малеев В.В. Районирование Африканской природноочаговой провинции в отношение филовирусных лихорадок. Вестник РАМН. 2017; 72 (5): 325–335. https://doi.org/10.15690/vramn804.

54. Щелканов М.Ю., Magassouba N’F., Boiro M.Y., Малеев В.В. Причины развития эпидемии лихорадки Эбола в Западной Африке. Лечащий врач. 2014; 11: 30–36.

55. Mariappan V., Pratheesh P., Shanmugam L. et al. Viral hemorrhagic fever: molecular pathogenesis and current trends of disease management – an update. Current research in virological science. 2021; 2: 100009. doi:10.1016/j.crivro.2021.100009.

56. 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

57. Barrientos L.G., Lasala F., Otero J.R. et al. In vivo evaluation of cyanovirin-N antiviral activity, by use of lentiviral vectors with Filovirus envelope glycoproteins. J. of Infectious Diseases. 2004; 189 (8): 1440–1443. doi:10.1086/382658

58. Garrison A.R., Giomarelli B.G., Lear-Rooney C.M. et al. The cyanobacterial lectin scytovirin displays potent in vitro and in vivo against Zaire Ebola virus. Antivirus Res. 2014; 10: 1–7. doi:10.1016/j.antiviral.2014.09.0123

59. Mitchell C.A., Ramessar K., O’Keefe B.R. Antiviral lectins: selective inhibitors of viral entry. Antiviral Research. 2017; 142: 37–54. doi:10.1016/j.antiviral.2017.03.007

60. Liu J., ObaidiI., Nagar S. et al. The antiviral potential of algal-derived macromolecules. 2021; 3: 120–134. doi:10.1016/j.crbiot.2021.04.003

61. Карамов Э.В., Горбачева А.П., Корнилаева Г.В., Лукьянова Н.С., Пашкова Т.А., Щелканов М.Ю., Ярославцева Н.Г. Изучение молекулярных механизмов вирусиндуцированного слияния мембран. Информационный бюллетень Российского фонда фундаментальных исследований. 1995; 3 (4): 361.

62. Shchelkanov M.Yu., Yudin A.N., Antonov A.V. et al. Variability Analysis of HIV-1 gp120 V3 Region: I. Point Estimators for the Amino Acid Distribution Characteristics. Journal of Biomolecular Structure and Dynamics. 1997 a; 15 (2): 217–229. doi:10.1080/07391102.1997.10508187

63. Coulibaly F.S., Thomas D.N., Youan B-B. Anti HIV lectins and current delivery strategies. AIMS Molecular Science. 2018; 5 (1): 96–116. doi:10.3934/molsci.2018.1.96.

64. Karamov E.V., Yaroslavtseva N.G., Shchelkanov M.Yu. et al. Antigenic and genetic relations between different HIV-1 subtypes in Russia. Immunology and Infectious Diseases. 1996; 6: 15–24. (In Russ.).

65. Bbosa N, Kaleebu P, Ssemwanga D. HIV subtype diversity worldwide. Curr. Opin. HIV AIDS. 2019; 14 (3): 153-160. doi:10.1097/COH.0000000000000534

66. Shchelkanov M.Yu., Yudin A.N., Antonov A.V. et al. Variability Analysis of HIV-1 gp120 V3 Region: II. Hierarchy of taxons. Journal of Biomolecular Structure and Dynamics. 1997 b; 15 (2): 231–241. doi:10.1080/07391102.1997.10508188

67. Martin-Moreno A., Munoz-Fernandez A. Dendritic cells, the double agent in the war against HIV-1. Front. Immunol. 2019. doi:10.3389/fimmu.2019.02485.

68. Esser M.T., Mori T., Mondor I. et al. Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J. Virol. 1999; 73: 4360–4371.

69. Buffa V., Stieh D., Mamhood N. et al. Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models. J. Gen. Virol. 2009; 90: 234–243. doi:10.1099/vir.0.004358-0

70. Щелканов М.Ю., Ярославцева Н.Г., Емельянов А.В., Сахурия И.Б., Абэлян А.В., Верёвочкин С.В., Козлов А.П., Карамов Э.В. Модель функционирования верхушечного эпитопа V3-петли gp120 ВИЧ-1 в составе комплекса с антителами. Молекулярная биология. 1998; 32 (6): 1062–1074.

71. Obiero J.P, Ogongo P., Mwethera C., Wiysonge S. Микробициды для местного применения для профилактики инфекций, передающихся половым путем. Cochrane Database of Systematic Reviews. 2021. doi:10.1002/14651858.CD007961.pub3

72. Жернов Ю.В., Хаитов М.Р. Микробициды для топической иммунопрофилактики ВИЧ-инфекции. Бюлл. Сибирской медицины. 2019; 18 (1): 49–59. https://doi.org/10.20538/1682-0363-2019-1-49-59.

73. Boyd M.R., Gustafson K.R., McMahon J.B. et al. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob agent Chemother. 1997; 41: 1521–1530.

74. Pagarete A., Ramos A.S., Puntervoll P. et al. Antiviral potential of algal metabolites – a comprehensive review. Mar. Drugs. 2021; 19 (2): 94. doi:10.3390/md19020094

75. Tsai C-C., Emau P., Jiang Y. et al. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res. And Human Retroviruses 2004; 20 (1). doi:10.1089/088922204322749459.

76. Balzarini J. Inhibition of HIV entry by carbohydrate-binding proteins. Antiviral Res. 2006; 7 (2–3): 237–247. doi:10.1016/j.antiviral.2006.02.004.

77. Huskens D., Vermeire K., Vandemeulebroucke E., Balzarini J., Schols D. Safety concerns for the potential use of cyanovirin-N as a microbicidal anti-HIV agent. Int. J. Biochem. 2008; 40 (12): 2804–28014. doi:10.1016/j.biocel.2008.05.023.

78. Chen J., Huang D. Linker-extended native cyanovirin-N facilitates PEGylation and potently inhibits HIV-1 targeting the glycan ligand. PLoS One. 2014; 9 (1): e86455. doi:10.1371/journal.pone.0086455.

79. Akkouh O., Ng T.B., Singh S.S. et al. Lectins with anti-HIV activity: a review. Molecules. 2015; 6 (20): 648–668. doi:10.3390/molecules20010648.

80. Huskens D., Ferir K., Vermeire J. et al. Microvirin, a novel α (1,20-mannose-specific lectin isolated from Microcystis aeruginosa, has anti-HIV1 activity comparable with than of cyanovirin-N but a much higher safety profile. Microbiology. 2010; 285 (32): 24845–24854. doi:10.1074/jbc.M110.128546.

81. Shahid M., Qadir A., Yang J. et al. An engineered microvirin variant with identical structural domains potently inhibits human immunodeficiency virus and hepatitis C virus cellular entry. Viruses. 2020; 12 (2): 199. doi:10.3390/v12020199.

82. Lagenaur L.A., Swedek I., Lee P.P., Parks T.P. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women. PLoS One. 2015; 10 (4): e0122730. doi:10.1371/journal.pone.0122730.

83. Lofti H., Sheervalilo R., Zarghami N. An update of the recombinant protein expression systems of cyanovirin-N and challenges of preclinical development. Bioimpacts. 2018; 8: 139–151. doi:10.15171/bi.2018.16.

84. Madeira L.M., Szeto T.H., Ma J.K-C., Drake P.M.W. Rhizosecretion improves the production of cyanovirin-N in Nicotiana tabacum through simplified downstream processing. Biotechnol. J. 2016; 11 (7): 910–919. doi:10.1002/biot.201500371.

85. J’Keefe B.R., Murad A.M., Vianna G.R. et al. Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV. Plant Biotechnol. J. 2015; 13: 884–892.

86. Armario-Najera V., Blanco-Perera A, Shenoy S.R. et al. Physicochemical characterization of the recombinant lectin scytovirin and microbicidal activity of the SD1 domain produced in rice against HIV-1. Plant Cell Reports. 2022; 41: 1013–1023.

87. Рахманова А.Г., Яковлев А.А., Кащенко В.А., Шаройко В.В. Хронический вирусный гепатит С и цирроз печени. Руководство для врачей. С-Пб.: СпецЛит. 2016; 380.

88. Kim C.W., Chang K.M. Hepatitis C virus: virology and life cycle. Clin. Mol. Hepatol 2013; 19: 17–125.

89. Соколова Т.М. Вирус гепатита С (Flaviviridae: Hepacivirus C): регуляция сигнальных реакций врожденного иммунитета. Вопросы вирусологии. 2020; 65 (6): 307–1316. https://doi.org/10.36233/0507-4088-2020-65-6-1.

90. Benedicto I., Gondar V., Molina-Jimenez J. et al. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J. Virol. 2015; 89: 4180–4190.

91. Krey T., Alayer J., Kikuti C.M. et al. The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule. PLoS Pathog. 2010: e10000762.

92. Guo Y., Yu H., Zhong Y. et al. Lectin microarray and mass spectrometric analysis of hepatitis C proteins reveals N-linked glycosylation. Medicine. 2018; 97 (15): e0208. doi:10.1097/MD.0000000000010208.

93. Kachko A., Loesgen S., Shazad-Ul-Hussan S. et al. Inhibition of hepatitis C virus by the cyanobacterial protein Microcystis viridis lectin: mechanistic differences between the high-mannose specific lectins MVL, CV-N, and GNA. Mol. Pharm. 2013; 10 (12): 4590–4602. doi:10.1021/mp400399b.

94. Ito S., Ikuno T., Mishima et al. In vitro human helper T-cell assay to screen antibody drug candidates for immunogenicity. J. of Immunotoxicology. 2019; 16: 125-132.

95. Min Y.Q., Duan X-C., Zhou Y-D. Effects of microvirin monomers and oligomers on hepatitis C virus. Bioscience Reports. 2017; 37 BSR20170015. doi:10.1042/BSR20170015.

96. Takebe Y., Saucedo C.J., Lund G. et al. Antiviral lectins from red and bluegreen algae show potent in vitro and in vivo activity against hepatitis C virus. PLoS One. 2013; 8 (5): e64449. doi:10.1371/journal.pone.0064449.

97. Carpine R., Sieber S. Antibacterial and antiviral metabolites from cyanobacteria: their application and their impact on human health. Current Research in Biotechnology. 2021; 3: 65–81. doi:10.1016/j.crbiot.2021.03.001.

98. Izquierdo L., Oliveira C., Fournier C. et al. Hepatitis C virus resistance to carbohydrate-binding agents. PLoS ONE 2016; 11 (2): e0149064. doi:10.1371/journal.pone.0149064.

99. Murphy P.V., André S., Gabius H.J. The third dimension of reading the sugar code by lectins: design of glycoclusters with cyclic scaffolds as tools with the aim to define correlations between spatial presentation and activity. Molecules. 2013; 18: 4026–4053. doi:10.3390/molecules18044026

100. Kaltner H., Gabius H.J. A toolbox of lectins for translating the sugar code: the galectin network in phylogenesis and tumors. Histol Histopathol. 2012; 27: 397–416. doi:10.14670/hh-27.397

101. Saad A.A. Recombinant lectins as pioneering anti-viral agents against COVID-19. Hematol. Transfus. Int. J. 2021; 9 (4): 77–79. doi:10.15406/htij.2021.09.00259

102. Swanson M.D., Boudreaux D.M., Salmon L. et al. Engineering therapeutic lectin by uncoupling mitogenicity from antiviral activity. Cell. 2015; 163 (3): 746–758. doi:10.1016/j.cell.2015.09.058.

103. Coves-Datson E.M. Dyall J., DeWald L.E. et al. Inhibition of Ebola virus by molecularly engineered banana lectin. PLoS Negl. Trop. Dis. 2019; 13: e0007595;

104. Coves-Datsdon E.M., King S.R. Legendre M. et al. A molecvularly engineered antiviral banana lectin inhibits fusion and is efficacious against influenza virus infection in vivo. Proc. Natl. Acad. Sci. USA. 2020; 117 (4): 2122–2132. doi:10.1073/pnas.1915152117.

105. Konozy E., Osman M., Dirar A. Plant lectins as potent anti-coronaviruses, anti-inflammatory, antinoceptive and antiulcer agents. Saudi J. of Biological Sciences. 2022; 29 (6): 103301. doi:/10.1016/j.sjbs.2022.103301.

106. Encarnacao T., Pais A.C.C., Campos M.G. et al. Cyanobacteria and microalgae: a renewable source of bioactive compounds and other chemicals. Science Progress. Research Article. 2015. doi:10.3184/003685015X14298590596266

107. Pradhan B., Nayak R., Patra S. et al. Cyanobacteria and algae-derived bioactive metabolites as antiviral agents: evidence, mode of action, and scope for furth expansion; a comprehensive review in light of the SARSCoV-2 outbreak. Antioxidants/ 2022-02-11, doi:10.3390/antiox11020354.