vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2021-18-4-497-512vestim-808Research ArticleОБЗОРЫREVIEWSCOVID-19: характеристика возбудителя, механизмы естественного и адаптивного иммунного ответа, генетическое разнообразие и распространениеCOVID-19: pathogen characteristics, natural and adaptive immune response mechanisms, genetic diversity and distributionТитовЛ. П.TitovL. P.

Титов Леонид Петрович ‒ член-корреспондент, д-р мед. наук, профессор, заведующий лабораторией

ул. Филимонова, 23, 220114, г. Минск

Leonid Р. Titov ‒ Corresponding Member, D. Sc. (Med.), Professor, Head of the Laboratory

23, Filimonov Str., 220114, Minsk

leotit310@gmail.comСпринджукМ. В.SprindzukM. V.

Спринджук Матвей Владимирович ‒ канд. техн. наук

ул. Сурганова, 6, 220012, г. Минск

Matvey V. Sprindzuk ‒ Ph. D. (Eng.)

6, Surganov Str., 220012, Minsk

Республиканский научно-практический центр эпидемиологии и микробиологииRepublican Scientific and Practical Center for Epidemiology and MicrobiologyОбъединенныей институт проблем информатики НАН БеларусиUnited Institute of Informatics Problems of the National Academy of Sciences of Belarus202104122021184497512Copyright © Титов Л.П., Спринджук М.В., 20212021Титов Л.П., Спринджук М.В.Titov L.P., Sprindzuk M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/808

COVID-19 – пандемически распространяющееся заболевание, вызываемое представителем семейства Coronaviridae – бета-2 короновирусом, получившим название SARS-CoV-2. Продолжающаяся пандемия COVID-19 нанесла серьезный урон состоянию здоровья населения нашей планеты – на начало июля 2021 г. заболело более 187,9 млн человек. От инфекции скончались более 4,0 млн пациентов (>2,0 %). В статье рассматриваются критически значимые молекулярно-генетические аспекты биологии возбудителя (строение +РНК генома, свойства белков), важные для понимания механизмов развития болезни, гуморальные и клеточные механизмы индивидуальной и коллективной иммунологической защиты, генетическая изменчивость вируса, принципы и платформы по созданию вакцин.

COVID-19 is a pandemic disease caused by a member of the Coronaviridae family, a beta-2 coronavirus named SARS-CoV-2. The COVID-19 pandemic lasting about 19 months has caused serious damage to the health of people on our planet – by the 13 of July 2021, more than 187.9 000 000 patients have been diagnosed and more than 4.0 mln patients died from infection (> 2.0 %). Scientists around the world are actively investigating the critically important molecular-genetic aspects of the biology of the pathogen (genome RNA structure, proteins properties) that are important for understanding the disease mechanisms, as well as the mechanisms of individual and collective immunological protection and vaccines development with non-specific prophylactics.

COVID-19коронавирус SARS-CoV-2иммунитетгенотипывакциныCOVID-19coronavirus SARS-CoV-2immunitygenotypesvaccinesReferencesA novel coronavirus from patients with pneumonia in China, 2019 / N. Zhu [et al.] // N. Eng. J. Med. – 2020. – Vol. 382, N 8. – P. 727–733. https://doi.org/10.1056/NEJMoa2001017Zhu N., Zhang D., Wang W., Li X., Yang B., Song J. [et al.]. A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine, 2020, vol. 382, no. 8, pp. 727–733. https://doi.org/10.1056/NEJMoa2001017Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China / C. Huang [et al.] // Lancet. – 2020. – Vol. 395, N 10223. – P. 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. [et al.]. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, vol. 395, no. 10223, pp. 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5Львов, Д. К. Истоки пандемии COVID-19: экология и генетика коронавирусов (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (подрод Sarbecovirus), MERS–CoV (подрод Merbecovirus) / Д. К. Львов, С. В. Альховский // Вопросы вирусологии. – 2020. – Т. 65, № 2. – С. 62–70.L’vov D. K., Al’khovskii S. V. Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS–CoV (subgenus Merbecovirus). Voprosy virusologii [Virology issues], 2020, vol. 65, no. 2, pp. 62–70 (in Russian).Харченко, Е. П. Коронавирус SARS-CoV-2: особенности структурных белков, контагиозность и возможные иммунные коллизии / Е. П. Харченко // Эпидемиология и вакцинопрофилактика. – 2020. – Т. 19, № 2. – С. 13–30. https://doi.org/10.31631/2073-3046-2020-20-2-13-30Kharchenko E. P. The Coronavirus SARS-Cov-2: the characteristics of structural proteins, contagiousness, and possible immune collisions. Epidemiologiya i vaktsinoprofilaktika [Epidemiology and vaccinal prevention], 2020, vol. 19, no. 2, pp. 13–30 (in Russian). https://doi.org/10.31631/2073-3046-2020-20-2-13-30Титов, Л. П. Вирусология: терминологический словарь / Л. П. Титов. – Минск : Минсктиппроект, 2009. – 445 с.Titov L. P. Virology: Terminological dictionary. Minsk, Minsktipproekt Publ., 2009. 445 p. (in Russian).SARS-CoV-2 envelope and membrane proteins: structural differences linked to virus characteristics? / M. Bianchi [et al.] // BioMed Res. Int. – 2020. – Vol. 2020. – Art. ID 4389089. https://doi.org/10.1155/2020/4389089Bianchi M., Benvenuto D., Giovanetti M., Angeletti S., Ciccozzi M., Pascarella S. SARS-CoV-2 envelope and membrane proteins: structural differences linked to virus characteristics? BioMed Research International, 2020, vol. 2020, art. ID 4389089. https://doi.org/10.1155/2020/4389089Update vision on COVID-19: structure, immune pathogenesis, treatment and safety assessment / R. Agrahari [et al.] // Sensors Int. – 2021. – Vol. 2. – Art. 100073. https://doi.org/10.1016/j.sintl.2020.100073Agrahari R., Mohanty S., Vishwakarma K., Nayak S. K., Samantaray D., Mohapatra S. Update vision on COVID-19: structure, immune pathogenesis, treatment and safety assessment. Sensors International, 2021, vol. 2, art. 100073. https://doi. org/10.1016/j.sintl.2020.100073Minireview of progress in the structural study of SARS-CoV-2 proteins / G. Zhu [et al.] // Curr. Res. Microb. Sci. – 2020. – Vol. 1. – P. 53–61. https://doi.org/10.1016/j.crmicr.2020.06.003Zhu G., Zhu C., Zhu Y., Sun F. Minireview of progress in the structural study of SARS-CoV-2 proteins. Current Research in Microbial Sciences, 2020, vol. 1, pp. 53–61. https://doi.org/10.1016/j.crmicr.2020.06.003Su, S. A suspicious role of interferon in the pathogenesis of SARS-CoV-2 by enhancing expression of ACE2 / S. Su, S. Jiang // Signal Transduct. Target Ther. – 2020. – Vol. 5, N 71. – P. 1–2. https://doi.org/10.1038/s41392-020-0185-zSu S., Jiang S. A suspicious role of interferon in the pathogenesis of SARS-CoV-2 by enhancing expression of ACE2. Signal Transduction and Targeted Therapy, 2020, vol. 5, no. 71, pp. 1–2. https://doi.org/10.1038/s41392-020-0185-zDistribution of ACE2, CD147, CD26 and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors / U. Radzikowska [et al.] // Allergy. – 2020. – Vol. 75, N 11. – P. 2829–2845. https://doi.org/10.1111/all.14429Radzikowska U., Ding M., Tan G., Zhakparov D., Peng Y., Wawrzyniak P. [et al.]. Distribution of ACE2, CD147, CD26 and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors. Allergy, 2020, vol. 75, no. 11, pp. 2829–2845. https://doi.org/10.1111/all.14429Титов, Л. П. Медицинская геномика: организация генома, регуляция экспрессии генов, генетическая вариабельность / Л. П. Титов // Вес. Нац. aкад. навук Беларусі. Сер. мед. навук. – 2015. ‒ № 4. – С. 97–113.Titov L. P. Medical genomics: human genome organization, gene expression regulation and genetic variability. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seryya meditsinskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2015, no. 4, pp. 97–113 (in Russian).Kaushic, C. Understanding immune responses to SARS-CoV-2 / C. Kaushic // RSC COVID-19 series. – 2020. ‒ N 28. – P. 1–14.Kaushic C. Understanding immune responses to SARS-Cov-2. RSC COVID-19 series, 2020, no. 28, pp. 1–14.Coronavirus biology and replication: implications for SARS-CoV-2 / P. V’kovski [et al.] // Nat. Rev. Microbiol. – 2020. – Vol. 19, N 3. – P. 155–170. https://doi.org/10.1038/s41579-020-00468-6V’kovski P., Kratzel A., Steiner S., Stalder H., Thiel V. Coronavirus biology and replication: implications for SARSCov-2. Nature Reviews Microbiology, 2020, vol. 19, no. 3, pp. 155–170. https://doi.org/10.1038/s41579-020-00468-6Титов, Л. П. Генетика и вирулентность вирусов / Л. П. Титов // Проблемы бактериологии и иммунологии : материалы юбил. науч. конф. (к 80-летию кафедры микробиологии, вирусологии, иммунологии БГМУ) / под ред. Л. П. Титова. – Минск, 2005. – С. 106–115.Titov L. P. Genetics and virulence of viruses. Problemy bakteriologii i immunologii : materialy yubileinoi nauchnoi konferentsii k 80-letiyu kafedry mikrobiologii, virusologii, immunologii BGMU (6 fevralya 2004 goda, Minsk) [Problems ofТитов, Л. П. Противовирусный иммунитет: молекулярно-клеточные механизмы, закономерности развития и иммунопатология / Л. П. Титов, И. А. Карпов // Мед. журн. – 2007. – № 1. – С. 1–31.bacteriology and immunology: materials of the jubilee scientific conference dedicated to the 80th anniversary of the Department of Microbiology, Virology, Immunology, BSMU (February 6, 2004, Minsk)]. Minsk, 2005, pp. 106–115 (in Russian).Immune responses and immunity to SARS-CoV-2 [Электронный ресурс]. – Режим доступа: https://www.ecdc. europa.eu/en/covid–19/latest–evidence/immune– responses. – Дата доступа: 20.04.2021.Titov L. P., Karpov I. A. Antiviral immunity: molecular and cellular mechanisms, patterns of development and immunopathology. Meditsinskii zhurnal [Medical journal], 2007, no. 1, pp. 1–31 (in Russian).SARS-CoV-2 antibody testing-questions to be asked / M. K. Özçürümez [et al.] // J. Allergy Clin. Immunol. – 2020. – Vol. 146, N 1. – P. 35–43. https://doi.org/10.1016/j.jaci.2020.05.020Immune responses and immunity to SARS-CoV-2 (2021). Available at: https://www.ecdc.europa.eu/en/covid–19/latest–evidence/immune–responses (accessed 20.04.2021).Пащенков, М. В. Иммунный ответ против эпидемических коронавирусов / М. В. Пащенков, Р. М. Хаитов // Иммунология. – 2020. – Т. 41, № 1. – С. 5–18.Özçürümez M. K., Ambrosch A., Frey O., Haselmann V., Holdenrieder S., Kiehntopf M. [et al.]. SARS-CoV-2 antibody testing-questions to be asked. Journal of Allergy and Clinical Immunology, 2020, vol. 146, no. 1, pp. 35–43. https://doi. org/10.1016/j.jaci.2020.05.020Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients / C. M. Poh [et al.] // Nat. Commun. – 2020. – Vol. 11, N 2806. – P. 1–7. https://doi.org/10.1038/s41467-020-16638-2Pashchenkov M. V., Khaitov R. M. Immune response against epidemic coronaviruses. Immunologiya [Immunology], 2020, vol. 41, no. 1, pp. 5–18 (in Russian).SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses / U. Stervbo [et al.] // bioRxiv. – 2020. – 16 p. https://doi.org/10.1101/2020.07.01.182741Poh C. M., Carissimo G., Wang B., Amrun S. N., Lee C. Y.-P., Chee R. S.-L. [et al.]. Two linear epitopes on the SARSCoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nature Communications, 2020, vol. 11, no. 2806, pp. 1–7. https://doi.org/10.1038/s41467-020-16638-2T cells: warriors of SARS-CoV-2 infection / P. de Candia [et al.] // Trends Immunol. – 2021. – Vol. 42, N 1. – P. 18–30. https://doi.org/10.1016/j.it.2020.11.002Stervbo U., Rahmann S., Roch T., Westhoff T., Babel N. SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses. bioRxiv, 2020. 16 p. https://doi.org/10.1101/2020.07.01.182741Cell-mediated immune responses to COVID-19 infection / A. Guihot [et al.] // Front. Immunol. – 2020. – Vol. 11. – Art. 1662. https://doi.org/10.3389/fimmu.2020.01662de Candia P., Prattichizzo F., Garavelli S., Matarese G. T cells: warriors of SARS-CoV-2 infection. Trends in Immunology, 2021, vol. 42, no. 1, pp. 18–30. https://doi.org/10.1016/j.it.2020.11.002Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19 / A. K. Azkur [et al.] // Allergy. – 2020. – Vol. 75, N 7. – P. 1564–1581. https://doi.org/10.1111/all.14364Guihot A., Litvinova E., Autran B., Debré P., Vieillard V. Cell-mediated immune responses to COVID-19 infection. Frontiers in Immunology, 2020, vol. 11, art. 1662. https://doi.org/10.3389/fimmu.2020.01662Gutierrez, L. Deciphering the TCR repertoire to solve the COVID-19 Mystery / L. Gutierrez, J. Beckford, H. Alachkar // Trends Pharmacol. Sci. – 2020. – Vol. 41, N 8. – P. 518–530. https://doi.org/10.1016/j.tips.2020.06.001Azkur A. K., Akdis M., Azkur D., Sokolowska M., Veen W., Brüggen M., O’Mahony L., Gao Y., Nadeau K., Akdis C. Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19. Allergy, 2020, vol. 75, no. 7, pp. 1564–1581. https://doi.org/10.1111/all.1436424Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study / S. Stringhini [et al.] // Lancet. – 2020. – Vol. 396, N 10247. – P. 1–7. https://doi.org/10.1016/S0140-6736(20)31304-0Gutierrez L., Beckford J., Alachkar H. Deciphering the TCR repertoire to solve the COVID-19 mystery. Trends in Pharmacological Sciences, 2020, vol. 41, no. 8, pp. 518–530. https://doi.org/10.1016/j.tips.2020.06.001Prevalence of SARS-CoV-2 in Spain (ENE–COVID): a nationwide, population-based seroepidemiological study / M. Pollán [et al.] // Lancet. – 2020. – Vol. 396, N 10250. – P. 1–11. https://doi.org/10.1016/S0140-6736(20)31483-5Stringhini S., Wisniak A., Piumatti G., Azman A., Lauer S., Baysson H. [et al.]. Seroprevalence of anti- SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet, 2020, vol. 396, no. 10247, pp. 1–7. https://doi.org/10.1016/S0140-6736(20)31304-0SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution / H. Wang [et al.] // ACS Cent. Sci. – 2020. – Vol. 6, N 12. – P. 2238–2249. https://doi.org/10.1021/acscentsci.0c00742Pollán M., Perez-Gomez B., Pastor-Barriuso R., Oteo J., Hernán M., Pérez-Olmeda M. [et al.]. Prevalence of SARSCoV-2 in Spain (ENE–COVID): a nationwide, population-based seroepidemiological study. Lancet, 2020, vol. 396, no. 10250, pp. 1–11. https://doi.org/10.1016/S0140-6736(20)31483-5Титов, Л. П. Иммунология: терминологический словарь / Л. П. Титов. – М. : МИА, 2008. – 512 с.Wang H., Wu X., Zhang X., Hou X., Liang T., Wang D. [et al.]. SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution. ACS Central Science, 2020, vol. 6, no. 12, pp. 2238–2249. https:// doi.org/10.1021/acscentsci.0c00742Mudgal, R. Prospects for mucosal vaccine: shutting the door on SARS-CoV-2 / R. Mudgal, S. Nehul, S. Tomar // Hum. Vaccin. Immunother. – 2020. – Vol. 16, N 12. – P. 2921–2931. https://doi.org/10.1080/21645515.2020.1805992Titov L. P. Immunology: Terminological dictionary. Moscow, MIA Publ., 2008. 512 p. (in Russian).Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity / H. Flament [et al.] // Nat. Immunol. – 2021. – Vol. 22, N 3. – P. 322–335. https://doi.org/10.1038/s41590-021-00870-zMudgal R., Nehul S., Tomar S. Prospects for mucosal vaccine: shutting the door on SARS-Cov-2. Human Vaccines & Immunotherapeutics, 2020, vol. 16, no. 12, pp. 2921–2931. https://doi.org/10.1080/21645515.2020.1805992Анализ перспективных направлений создания вакцин против COVID-19 / Г. Г. Онищенко [и др.] // БИОпрепараты. Профилактика, диагностика, лечение. – 2020. – Т. 20, № 4. – С. 216–227.Flament H., Rouland M., Beaudoin L., Toubal A., Bertrand L., Lebourgeois S. [et al.]. Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity. Nature Immunology, 2021, vol. 22, no. 3, pp. 322–335. https://doi. org/10.1038/s41590- 021-00870-zCOVID-19 vaccine [Электронный ресурс]. – Режим доступа: https://en.wikipedia.org/wiki/COVID–19_vaccine. – Дата доступа: 20.04.2021.Onishchenko G. G., Sizikova T. E., Lebedev V. N., Borisevich S. V. Analysis of promising approaches to COVID-19 vaccine development. Biopreparaty. Profilaktika, diagnostika, lechenie [BIOpreparations. Prevention, diagnosis, treatment], 2020, vol. 20, no. 4, pp. 216–227 (in Russian).Huang, Q. SARS-CoV-2 virus: vaccines in development / Q. Huang, J. Yan // Fund. Res. – 2021. – Vol. 1, N 2. – P. 131–138. https://doi.org/10.1016/j.fmre.2021.01.009COVID-19 vaccine (2021). Available at: https://en.wikipedia.org/wiki/COVID– 19_vaccine (accessed 20.04.2021).Intranasal immunization with inactivated SARS-CoV (SARS-associated coronavirus) induced local and serum antibodies in mice / D. Qu [et al.] // Vaccine. – 2005. – Vol. 23, N 7. – P. 924–931. https://doi.org/10.1016/j.vaccine.2004.07.031Huang Q., Yan J. SARS-CoV-2 virus: vaccines in development. Fundamental Research, 2021, vol. 1, no. 2, pp. 131– 138. https://doi.org/10.1016/j.fmre.2021.01.009Characteristics of SARS-CoV-2 and COVID-19 / B. Hu [et al.] // Nat. Rev. Microbiol. – 2021. – Vol. 19, N 3. – P. 141– 154. https://doi.org/10.1038/s41579-020-00459-7Qu D., Zheng B., Yao X., Guan Y., Yuan Z.-H., Zhong N.-S., Lu L.-W., Xie J.-P., Wen Y.-M. Intranasal immunization with inactivated SARS-CoV (SARS-associated coronavirus) induced local and serum antibodies in mice. Vaccine, 2005, vol. 23, no. 7, pp. 924–931. https://doi.org/10.1016/j.vaccine.2004.07.031Phylogenetic network analysis of SARS-CoV-2 genomes / P. Forster [et al.] // PNAS. – 2020. – Vol. 117, N 17. – P. 9241–9243. https://doi.org/10.1073/pnas.2004999117Hu B., Guo H., Zhou P., Shi Z.-L. Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews. Microbiology, 2021, vol. 19, no. 3, pp. 141–154. https://doi.org/10.1038/s41579-020-00459-7Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries / X. Yang [et al.] // Emerg. Microbiol. Infect. – 2020. – Vol. 9, N 1. – P. 1287–1299. https://doi.org/10.1080/22221751. 2020.1773745Forster P., Forster L., Renfrew C., Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proceedings of the National Academy of Sciences, 2020, vol. 117, no. 17, pp. 9241–9243. https://doi.org/10.1073/pnas.2004999117A global analysis of replacement of genetic variants of SARS-CoV-2 in association with containment capacity and changes in disease severity / Z. Chen [et al.] // Clin. Microbiol. Infect. – 2021. – Vol. 27, N 5. – P. 750–757. https://doi. org/10.1016/j.cmi.2021.01.018Yang X., Dong N., Chan E. W.-C., Chen S. Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries. Emerging Microbes and Infections, 2020, vol. 9, no. 1, pp. 1287–1299. https://doi.org/10.1080/22221751.2020.1773745Abduljalil, J. Epidemiology, genome, and clinical features of the pandemic SARS- Cov-2: a recent view / J. Abduljalil, B. Abduljalil // New Microb. New Infect. – 2020. – Vol. 35. – P. 100672. https://doi.org/10.1016/j.nmni.2020.100672Chen Z., Chong K. C., Wong M. C. S., Boon S. S., Huang J., Wang M. H., Ng R. W. Y., Lai C. K. C., Chan P. K. S. A global analysis of replacement of genetic variants of SARS-CoV-2 in association with containment capacity and changes in disease severity. Clinical Microbiology and Infection, 2021, vol. 27, no. 5, pp. 750–757. https://doi.org/10.1016/j.cmi.2021.01.018A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology / A. Rambaut [et al.] // Nat. Microbiol. – 2020. – Vol. 5, N 11. – P. 1403–1407. https://doi.org/10.1038/s41564-020-0770-5Abduljalil J., Abduljalil B. Epidemiology, genome, and clinical features of the pandemic SARS-Cov-2: a recent view. New Microbes and New Infect, 2020, vol. 35, p. 100672. https://doi.org/10.1016/j.nmni.2020.100672Титов, Л. П. Геномико-протеомические основы эволюции и молекулярной эпидемиологии вирусов / Л. П. Титов, В. И. Вотяков // Вес. Нац. aкад. навук Беларусі. Сер. мед. навук. ‒ 2011. – № 1. ‒ С. 109–124.Rambaut A., Holmes E. C., O’Toole Á., Hill V., McCrone J. T., Ruis C., du Plessis L., Pybus O. G. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nature Microbiology, 2020, vol. 5, no. 11, pp. 1403–1407. https://doi.org/10.1038/s41564-020-0770-5COVID-19 pandemic [Электронный ресурс]. – Режим доступа: https://en.wikipedia.org/wiki/COVID–19_ pandemic. – Дата доступа: 20.04.2021.Titov L. P., Votyakov V. I. Genomico-proteomical basis of the evolution and molecular epidemiology viruses, microorganisms and their biomacromolecules. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seryya meditsinskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2011, no. 1, pp. 109–124 (in Russian).COVID-19 pandemic in Belarus [Электронный ресурс]. – Режим доступа: https://en.wikipedia.org/wiki/ COVID–19_pandemic_in_Belarus. – Дата доступа: 20.04.2021.COVID-19 pandemic (2021). Available at: https://en.wikipedia.org/wiki/COVID– 19_pandemic (accessed 20.04.2021).COVID-19 pandemic in Belarus (2021). Available at: https://en.wikipedia.org/wiki/COVID–19_pandemic_in_Belarus (accessed 20.04.2021)COVID-19 pandemic in Belarus (2021). Available at: https://en.wikipedia.org/wiki/COVID–19_pandemic_in_Belarus (accessed 20.04.2021)

The authors declare that there are no conflicts of interest present.