Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI147010.15789/2220-7619-SPO-1470REVIEWSОБЗОРЫSome opportunities for immunotherapy in coronavirus infectionНекоторые возможности иммунотерапии при коронавирусной инфекцииhttps://orcid.org/0000-0002-2723-1496SmirnovV. S.СмирновВ. С.
Russian Federation

Smirnov Vyacheslav S., PhD, MD (Medicine), Professor, Leading Researcher, Laboratory Molecular Immunology, St. Petersburg Pasteur Institute; Head Researcher, JSC MВSPC “Cytomed”

197101, St. Petersburg, Mira str., 14

Смирнов Вячеслав Сергеевич, доктор медицинских наук, профессор, ведущий научный сотрудник лаборатории молекулярной иммунологии ФБУН НИИ эпидемиологии и микробиологии имени Пастера, главный научный сотрудник АО МБНПК «Цитомед»

197101, Санкт-Петербург, ул. Мира, 14

 

vssmi@mail.ruTotolianAreg A.ТотолянАрег А.
Russian Federation

Totolian Areg A., RAS Full Member, PhD, MD (Medicine), Professor, Head of the Department of Immunology, Pavlov First St. Petersburg State Medical University; Director, St. Petersburg Pasteur Institute

St. Petersburg

Тотолян Арег А., академик РАН, доктор медицинских наук, профессор, заведующий кафедрой иммунологии ГБОУ ВПО Первый Санкт-Петербургский Государственный медицинский университет им. акад. И.П. Павлова МЗ РФ; директор ФБУН НИИ эпидемиологии и микробиологии имени Пастера

Санкт-Петербург

totolian@pasteurorg.ruhttp://pasteurorg.ruSt-Petersburg Pasteur InstituteФБУН НИИ эпидемиологии и микробиологии им. ПастераJSC MBNPK “Cytomed”АО МБНПК «Цитомед»070820201034464582504202006052020Copyright ©; 2020, Smirnov V.S., Totolian A.A.Copyright ©; 2020, Смирнов В.С., Тотолян А.А.2020Smirnov V.S., Totolian A.A.Смирнов В.С., Тотолян А.А.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1470

Here we review means of immunomodulatory therapy for coronavirus infection caused by SARS-CoV-2 (COVID-19). It has been appreciated that highly limited arsenal of relatively effective means and methods of prevention and treatment of the COVID-19 pandemic is available. The goal of our study was to analyze some therapeutic approaches based on available publications for COVID-19 treatment viewed from acting via innate immunity system. Convalescent plasma serotherapy represents one of the means with verified therapeutic efficacy that was accompanied with decreased viral load and relief of the disease symptoms. The drawback of serotherapy results from limited number of potential plasma donors and profound variety in amount of SARS-CoV-2-specific antibodies found in donor plasma. Another approach to COVID-19 therapy is based on using monoclonal antibodies engineered to target specific virus antigenic determinants, most often surface spike antigen. Antibodies blocking such antigen are able to prevent virus entrance into target cells and development of overt infection. On the other hand, there are monoclonal antibodies abrogating production or binding of excessive amounts of pro-inflammatory cytokines, such as IL-6, TNFα, etc., some of which (tocilizumab) have been already tested in COVID-19 therapy, whereas the remaining preparations are being currently investigated and tested. A certain breakthrough in COVID-19 therapy was provided by the well-known drugs chloroquine and dihydrochloroquine, which have proven to be effective as antiviral, anti-inflammatory and immunomodulatory means. Finally, a new multicomponent immunomodulatory preparation Cytovir-3 has been proposed already passed clinical trials and recommended for use in prevention and treatment of influenza and SARS and might have found its own niche in preventing COVID-19, as SARS-CoV-2 also belongs to the group of acute respiratory viruses. Thus, the arsenal of means for COVID-19 prevention and treatment contains the drugs for immunomodulatory therapy and prevention of immune-related disorders developing in response to invasion pathogenic viruses and lowering a risk of possible damage. Hence, correct and scientifically justified use of such remedies will increase overall effectiveness of fight against the coronavirus pandemic.

Обзор посвящен анализу средств иммуномодулирующей терапии при коронавирусной инфекции, вызванной SARS-CoV-2 (COVID-19). Как известно, существует очень ограниченный арсенал относительно эффективных средств и методов профилактики и лечения COVID-19. Цель подготовленного обзора литературы — проанализировать некоторые терапевтические подходы к терапии COVID-19 с позиций воздействия на систему врожденного иммунитета. Одним из средств с доказанной терапевтической эффективностью является серотерапия плазмой, полученной из крови выздоравливающих больных. Показано, что переливание плазмы сопровождается сокращением вирусной нагрузки и купированием симптомов заболевания. Недостатком серотерапии является ограниченное количество потенциальных доноров плазмы и значительное варьирование содержания в донорской плазме титров специфических антител. Другим подходом к терапии является применение инженерных моноклональных антител против определенных антигенных детерминант вируса, чаще всего против поверхностного спайк-антигена. Антитела, блокирующие этот антиген, способны предотвратить проникновение вируса в клетку и развитие манифестной инфекции. Кроме того, имеются моноклональные антитела, предотвращающие выработку или связывающие избыточное количество провоспалительных цитокинов, таких как IL-6, TNFα и др. Некоторые из подобных антител (тоцилизумаб) уже испытаны при COVID-19, другие пока проходят исследования и испытания. Определенным прорывом в терапии стали хорошо известные препараты хлорохин и дигидрохлорохин, показавшие себя эффективными средствами противовирусной, противовоспалительной и иммуномодулирующей терапии. Наконец, был предложен новый поликомпонентный иммуномодулирующий препарат Цитовир-3, уже прошедший клинические испытания и рекомендованный к применению при профилактике и терапии гриппа и ОРВИ, который может найти свое место при профилактике COVID-19, поскольку возбудитель SARS-CoV-2 также относится к возбудителям острых респираторных вирусных инфекций. Таким образом, в арсенале средств профилактики и лечения COVID-19 имеются препараты для иммуномодулирующей терапии и профилактики иммунных нарушений, развивающихся в ответ на внедрение патогенного вируса и снижающих риск возможного ущерба. Правильное и научно обоснованное их применение позволит повысить эффективность борьбы с пандемией коронавирусной инфекции.

coronavirusSARS-CoVMERS-CoVCOVID-19serotherapyplasma of convalescentsmonoclonal antibodieschloroquinedihydrochloroquineCytovir-3коронавирусSARS-CoVMERS-CoVCOVID-19серотерапияплазма реконвалесцентовмоноклональные антителахлорохиндигидрохлорохинЦитовир-31. Вислобоков А.И., Мызников Л.В., Тарасенко А.А., Шабанов П.Д. Влияние дибазола и его новых производных на ионные каналы нейронов моллюска // Обзоры по клинической фармакологии и лекарственной терапии. 2013. Т. 11, № 3. С. 26–32.2. Смирнов В.С., Зарубаев В.В., Петленко С.В. Биология возбудителей и контроль гриппа и ОРВИ. СПб.: Гиппократ, 2020. 336 с.3. Смирнов В.С., Тотолян Арег А. Врожденный иммунитет при коронавирусной инфекции // Инфекция и иммунитет. 2020. Т. 10, № 2. С. 259–268. doi: 10.15789/2220-7619-III-14404. Соколова Т.М., Полосков В.В., Шувалов А.Н., Бурова О.С., Соколова З.А. Сигнальные TLR/RLR-механизмы иммуномодулирующего дей ствия препаратов ингавирин и тимоген // Российский биотерапевтический журнал. 2019. Т. 18, № 1. С. 60–66. doi: 10.17650/1726-9784-2019-18-1-60-665. Aguiar J.A., Tremblay B.J.-M., Mansfield M.J., Woody O., Lobb B., Banerjee A., Chan-diramohan A., Tiessen N., DvorkinGheva A., Revill S.,. Miller M.S., Carlsten C., Organ L., Joseph C., John A., Hanson P., McManus B.M., Jenkins G., Mossman K., Ask K., Doxey A.C., HirotaJ.A. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. bioRxiv, 2020: 030742. doi: 10.1101/2020.04.07.0307426. Anastassopoulou C., Russo L., Tsakris A., Siettos C. Data-based analysis, modelling and forecasting of the COVID-19 outbreak. PLoS One, 2020, vol. 15, no. 3: e0230405. doi: 10.1371/journal.pone.02304057. Arabi Y.M., Hajeer A.H., Luke T., Raviprakash K., Balkhy H., Johani S., Al-Dawood A., Al-Qahtani S., Al-Omari A., AlHameed F., Hayden F.G., Fowler R., Bouchama A., Shindo N., Al-Khairy K., Carson G., Taha Y., Sadat M., Alahmadi M. Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia. Emerg. Infect. Dis., 2016, vol. 22, no. 9, pp. 1554–1561. doi: 10.3201/eid2209.1511648. Battegay M., Kuehl R., Tschudin-Sutter S., Hirsch H.H., Widmer A.F., Neher R.A. 2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate — a word of caution. Swiss Med. Wkly, 2020, vol. 150: 20203. doi: 10.4414/smw.2020.202039. Boggu P., Venkateswararao E., Manickam M., Kwak D., Kim Y., Jung S.-H. Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB. Bioorg. Med. Chem., 2016, vol. 24, no. 8, pp. 1872–1878. doi: 10.1016/j.bmc.2016.03.01210. Bowie A.G., O’Neill L.A.J. Vitamin C inhibits NF-κB activation by TNF via the activation of p38 mitogen-activated protein kinase. J. Immunol., 2000, vol. 165, pp. 7180–7188. doi: 10.4049/jimmunol.165.12.718011. Carr A.C., Maggini S. Vitamin C and immune function. Nutrients, 2017, vol. 9, no. 11: E1211. doi: 10.3390/nu911121112. Casadevall A., Pirofski L.J. The convalescent sera option for containing COVID-19. Clin. Invest., 2020, vol. 130, no. 4, pp. 1545– 1548. doi: 10.1172/JCI13800313. Channappanavar R. Perlman S. Pathogenic human coronavirus infections: causes and con-sequences of cytokine storm and immunopathology. Semin. Immunopathol., 2017, vol. 39, pp. 529–539. doi: 10.1007/s00281-017-0629-x14. Chen L., Xiong J., Bao L., Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet. Infect. Dis., 2020, vol. 20, no. 4, pp. 398–400. doi: 10.1016/S1473-3099(20)30141-915. Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Biochem. Biophys. Res. Commun., 2020. doi: 10.1016/j.bbrc.2020.02.07116. Chinese Clinical Trial Register (ChiCTR) The world health organization international clinical trials registered organization registered platform. URL: http://www.chictr.org.cn/enIndex.aspx17. Coughlin M.M., Lou G., Martinez O., Masterman S.K., Olsen O.A., Moksa A.A., Farzan M., Babcook J.S., Prabhakara B.S., Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®. Virology, 2007, vol. 361, no. 1, pp. 93–102. doi: 10.1016/j.virol.2006.09.02918. Coughlin M.M., Prabhakar B.S. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action and therapeutic potential. Rev. Med. Virol., 2012, vol. 22, no. 1, pp. 2–17. doi: 10.1002/rmv.70619. COVID-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ, 2020, vol. 368: m1256. doi: 10.1136/bmj.m125620. Cowling B.J., Park M., Fang V.J., Wu P., Leung G.M., Wu J.T. Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015 separator commenting unavailable. Euro Surveil., 2015, vol. 20, no. 25. doi: 10.2807/1560-7917.es2015.20.25.2116321. De Clercq E. Potential antivirals and antiviral strategies against SARS coronavirus infections. Expert. Rev. Anti Infect. Ther., 2006, vol. 4, no. 2, pp. 291–302. doi: 10.1586/14787210.4.2.29122. Devaux C.A., Rolain J.M., Colson P., Raoulta D., New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int. J. Antimicrob. Agents, 2020: 105938. doi: 10.1016/j.ijantimicag.2020.10593823. Dyall J., Gross R., Kindrachuk J., Johnson R.F., Olinger G.G. Jr, Hensley L.E., Frieman M.B., Jahrling P.B. Middle east respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs, 2017, vol. 77, no. 18, pp. 1935–1966. doi: 10.1007/s40265-017-0830-1.24. Fantini J., Di Scala C., Chahinian H., Yahia N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int. J. Antimicrob. Agents, 2020: 105960. doi: 10.1016/j.ijantimicag.2020.10596025. Fehr А.R., Perlman S. Coronaviruses: an overview of their replication and pathogenes. Methods Mol. Biol., 2015, vol, 1282, pp. 1–23. doi: 10.1007/978-1-4939-2438-7_126. Feldmann M., Maini R.N., Woody J.N., Holgate S.T., Winter G., Rowland M., Richards D., Hussell T. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet, on line, 2020 April 09. doi: 10.1016/S0140-6736(20)30858-827. Ferraris O., Moroso M., Pernet O., Emonet S., Rembert A.F., Paranhos-Baccalà G., Peyrefitte C.N. Evaluation of CrimeanCongo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules. Antiviral Res., 2015, vol. 118, pp. 75–81. doi: 10.1016/j.antiviral.2015.03.00528. Fu B., Xu X., Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J. Transl. Med., 2020, vol. 18, p. 164. doi: 10.1186/s12967-020-02339-329. Gao J., Tian Z., Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioScience Trends, 2020, vol. 14, no. 1, pp. 72–73. doi: 10.5582/bst.2020.0104730. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M., Doudier B., Courjon J., Giordanengo V., Vieira V.E., Dupont H.T., Honoré S., Colson P., Chabrière E., La Scola B., Rolain J.M., Brouqui P., Raoulta D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents, 2020. doi: 10.1016/j.ijantimicag.2020.10594931. Giron C.C., Laaksonenc A.F. Barroso da Silva L. On the interactions of the receptor-binding domain of SARS-CoV-1 and SARSCoV-2 spike proteins with monoclonal antibodies and the receptor ACE2. bioRxiv, 2020: 026377. doi: 10.1101/2020.04.05.02637732. Gralinski L.E., Baric R.S. Molecular pathology of emerging coronavirus infections. J. Pathol., 2015, vol. 235, no. 2, pp. 185–195. doi: 10.1002/path.445433. Guo C., Li B., Ma H., Wang X., Cai P., Yu Q., Zhu L., Jin L., Jiang C., Fang J., Liu Q., Zong D. Zhang W., Lu Y., Li K., Gao X., Fu B., Liu L., Ma X., Weng J., Wei H., Jin T., Lin J., Qu K. Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis. bioRxiv, 2020: 029769. doi: 10.1101/2020.04.08.02976934. Guo Y.R., Cao Q.D., Hong Z.S., Tan Y.Y., Chen S.D., Jin H.J., Tan K.S., Wang D.Y.,Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak — an update on the status. Mil. Med. Res., 2020, vol. 7, p. 11. doi: 10.1186/s40779-020-00240-035. Huang X., Wei F., Hu L., Wen L., Chen K. Epidemiology and clinical characteristics of COVID-19. Arch. Iran Med., 2020, vol. 23, no. 4, pp. 268–271. doi: 10.34172/aim.2020.09.36. Hussell T., Pennycook A., Openshaw P.J. Inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopathology. Eur. J. Immunol., 2001, vol. 31, no. 9, pp. 2566–2673. doi: 10.1002/1521-4141(200109)31:93.0.co;2-l37. Jaume M., Yip M.S., Kam Y.W., Cheung C.Y., Kien F., Roberts A., Li P.H., Dutry I., Escriou N., Daeron M., Bruzzone R., Subbarao K., Peiris J.S.M., Nal B., Altmeyer R. SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. Hong Kong Med. J., 2012, vol. 18, suppl. 2, pp. 31–36.38. Keyaerts E., Vijgen L., Maes P., Neyts J., Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem. Biophys. Res. Commun., 2004, vol. 323, no. 1, pp. 264–268. doi: 10.1016/j.bbrc.2004.08.08539. Kotch C., Barrett D., Teachey D.T. Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert Rev. Clin. Immunol., 2019, vol. 15, no. 8, pp. 813–822. doi: 10.1080/1744666X.2019.162990440. Kuzmina N.A., Younan P., Gilchuk P., Santos R.I., Flyak A.I., Ilinykh P.A., Huang K., Lubaki N.M., Ramanathan P., Crowe J.E. Jr., Bukreyev A. Antibody-dependent enhancement of Ebola virus infection by human antibodies isolated from survivors. Cell Rep., 2018, vol. 24, no. 7, pp. 1802–1815.e5. doi: 10.1016/j.celrep.2018.07.03541. Lai C.C., Shih T.P., Ko W.C., Tang H.J., Hsueh P.R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int. J. Antimicrob. Agents., 2020, vol. 17: 105924. doi: 10.1016/j.ijantimicag.2020.10592442. Lee S.J., Silverman E., Bargman J.M. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat. Rev. Nephrol., 2011, vol. 7, no. 12, pp. 718–729. doi: 10.1038/nrneph.2011.15043. Letter to autorisation. FDA. USA, 2020, March 28. URL: https://www.fda.gov/media/136534/download44. Li G. Fan Y. Lai Y. Han T., Li Z., Zhou P., Pan P., Wang W., Hu D., Liu X., Zhang Q., Wu J. Coronavirus infections and immune responses. J. Med. Virol., 2020, vol. 92, pp. 424–432. doi: 10.1002/jmv.2568545. Li H., Liu S.M., Yu X.H., Tang S.L., Tang. C.-K. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int. J. Antimicrob. Agents, 2020: 105951. doi: 10.1016/j.ijantimicag.2020.105951.46. Li X., Geng M., Peng Y., Meng L., Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J. Pharm. Anal., 2020 Mar 5. doi: 10.1016/j.jpha.2020.03.00147. Lichtenstein L., Ron Y., Kivity S., Ben-Horin S., Israeli E., Fraser G.M., Dotan I., Chowers Y., Confino-Cohen R., Weiss B. Infliximab-related infusion reactions: systematic review. J. Crohns. Colitis, 2015, vol. 9, no.9. pp. 806–815. doi: 10.1093/ecco-jcc/jjv09648. Lo B., Zhang K., Lu W., Zheng L., Zhang Q., Kanellopoulou C., Zhang Y., Liu Z., Fritz J.M., Marsh R., Husami A., Kissell D., Nortman S., Chaturvedi V., Haines H., Young L.R., Mo J., Filipovich A.H., Bleesing J.J., Mustillo P., Stephens M., Rueda C.M., Chougnet C.A., Hoebe K., McElwee J., Hughes J.D., Karakoc-Aydiner E., Matthews H.F., Price S., Su H.C., Rao V.K., Lenardo M.J., Jordan M.B. Autoimmune disease. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science, 2015, vol. 349, no. 6246, pp. 436–40. doi: 10.1126/science.aaa166349. Magagnoli J., Narendran S., Pereira F., Cummings T.H., Hardin J.W., Sutton S.S., Ambati J. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19. Med, 2020. doi: 10.1016/j.medj.2020.06.00150. Mair-Jenkins J., Saavedra-Campos M., Baillie J.K., Cleary P., Khaw F.M., Lim W.S., Makki S., Rooney K.D., Convalescent Plasma Study Group, Nguyen-Van-Tam J.S., Beck C.R. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory metaanalysis. J. Infect. Dis., 2015, vol. 211, no. 1, pp. 80–90. doi: 10.1093/infdis/jiu39651. Malavolta M., Giacconi R., Brunetti D., Provinciali M., Maggi F. Exploring the Relevance of senotherapeutics for the current SARS-CoV-2 emergency and similar future global health threats. Cells, 2020, vol. 9, no. 4: E909. doi: 10.3390/cells904090952. Mason R.J. Pathogenesis of COVID-19 from a cell biology perspective. Eur. Respir. J., 2020, vol. 55, no. 4: 2000607. doi: 10.1183/13993003.00607-202053. Masters P.S. The molecular biology of coronaviruses. Adv. Vir. Res., 2006, vol. 66, pp. 193–292. doi: 10.1016/S0065-3527(06)66005-354. McCreary E.K., Pogue J.M. Coronavirus disease 2019 treatment: a review of early and emerging options. Open Forum Infect. Dis., 2020, vol. 7, no. 4: ofaa105. doi: 10.1093/ofid/ofaa10555. Mi L., Li W., Li M., Chen T., Wang M., Sun L., Chen Z. Immunogenicity screening assay development for a novel human-mouse chimeric anti-CD147 monoclonal antibody (Metuzumab). J. Immunol. Methods, 2016, vol. 433, pp. 38–43. doi: 10.1016/j.jim.2016.02.02256. Moss I.B., Moss M.B., dos Reis D.S., Coelho R.M. Immediate infusional reactions to intravenous immunobiological agents for the treatment of autoimmune diseases: experience of 2126 procedures in a non-oncologic infusion centre. Rev. Bras. Reumatol., 2014, vol. 54, no. 2, pp. 102–109.57. Mourad A.A., Boktor M.N., Yilmaz-Demirdag Y., Bahna S.L. Adverse reactions to infliximab and the outcome of desensitization. Ann. Allergy Asthma Immunol., 2015, vol. 115, no. 2, pp. 143–146. doi: 10.1016/j.anai.2015.06.00458. Paton N.I., Lee L., Xu Y., Ooi E.E., Cheung Y.B., Archuleta S., Wong G., Wilder-Smith A. Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. Lancet Infect. Dis., 2011, vol. 11, no. 9, pp. 677–683. doi: 10.1016/S1473-3099(11)70065-259. Pelegrin M., Naranjo-Gomez M., Piechaczyk M. Antiviral monoclonal antibodies: can they be more than simple neutralizing agents? Trends Microbiol., 2015, vol. 23, no. 10, pp. 653–665. doi: 10.1016/j.tim.2015.07.00560. Pereira B.B. Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of Coronavirus Disease 2019 (COVID-19) pandemic: a timely review. J. Toxicol. Environ. Health. B Crit. Rev., 2020, vol. 23, no. 4, pp. 177–181. doi: 10.1080/10937404.2020.175234061. Rajeshkumar N.V., Yabuuchi S., Pai S.G., Maitra A., Hidalgo M., Dang C.V. Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice. bioRxiv, 2020.03.31.018556. doi: 10.1101/2020.03.31.01855662. Rawaf S., Al-Saffar M.N., Quezada-Yamamoto H., Alshaikh M., Pelly M., Rawaf D., Dubois E. Majeed A. Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review. medRxiv, 2020: 47403194. doi: 10.1101/2020.05.07.20094326.t63. Roback J.D., Guarner J. Convalescent plasma to treat COVID-19: possibilities and challenges. JAMA, 2020 Mar 27. doi: 10.1001/jama.2020.494064. Russell B., Moss C., George G., Santaolalla A., Cope A., Papa S., Van Hemelrijck M. Associations between immunesuppressive and stimulating drugs and novel COVID-19 — a systematic review of current evidence. Ecancermedicalscience, 2020, vol. 14: 1022. doi: 10.3332/ecancer.2020.102265. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect. Dis., 2003, no. 11, pp. 722–727. doi: 10.1016/s1473-3099(03)00806-566. Savarino A., Gennero L., Sperber K., Boelaert J.R. The anti-HIV-1 activity of chloroquine. J. Clin. Virol., 2001, vol. 20, no. 3, pp. 131–135. doi: 10.1016/s1386-6532(00)00139-6.67. Şencan I., Kuzi S. Global threat of COVID 19 and evacuation of the citizens of different countries. Turk. J. Med. Sci., 2020, vol. 50, no. SI-1, pp. 534–543. doi: 10.3906/sag-2004-2168. Shang B., Wang X.Y., Yuan J.W., Vabret A., Wu X.D., Yang R.F., Tian L., Ji Y.Y., Deubel V., Suna B. Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus. Biochem. Biophys. Res. Commun., 2005, vol. 336, no. 1, pp. 110–117. doi: 10.1016/j.bbrc.2005.08.03269. Shanmugaraj B., Siriwattananon K., Wangkanont K., Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac. J. Allergy Immunol., 2020, vol. 38, no. 1, pp. 10–18. doi: 10.12932/AP-200220-077370. Sheppard M., Laskou F., Stapleton P.P., Hadavi S., Dasgupta B. Tocilizumab (Actemra). Hum. Vaccin. Immunother., 2017, vol. 13, no. 9, pp. 1972–1988. doi: 10.1080/21645515.2017.131690971. Singh S., Moore T.J. Efficacy and safety of hydroxychloroquine and chloroquine for COVID-19: a systematic review. medRxiv, 2020: 20106906. doi: 10.1101/2020.05.19.2010690672. Siu K.L., Yuen K.S., Castaño-Rodriguez C., Ye Z.W., Yeung M.L., Fung S.Y., Yuan S., Chan C.P., Yuen K.Y., Enjuanes L., Jin D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J., 2019, vol. 33, no. 8, pp. 8865–8877. doi: 10.1096/fj.201802418R73. Smits S.L., de Lang A., van den Brand J.M.A., Leijten L.M., van IJcken W.F., Eijkemans M.J.C., van Amerongen G., Kuiken T., Andeweg A.C., Osterhaus A.D.M.E., Haagmans B.L. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathog., 2010, vol. 6, no. 2: e1000756. doi: 10.1371/journal.ppat.100075674. Sohrabi C., Alsafi Z., O’Neill N., Khan M., Kerwan A., Al-Jabir A., Iosifidis C., Agha R. World health organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19). Int. J. Surg., 2020, vol. 76, pp. 71–76. doi: 10.1016/j.ijsu.2020.02.034C75. Su L., Ma X., Yu H., Zhang Z., Bian P., Han Y., Sun J., Liu Y., Yang C., Geng J., Zhang Z., Gai Z. The different clinical characteristics of corona virus disease cases between children and their families in China — the character of children with COVID-19. Emerg. Microbes Infect., 2020, vol. 9, no. 1 pp. 707–713. doi: 10.1080/22221751.2020.174448376. Tetro J.A. Is COVID-19 receiving ADE from other coronaviruses? Microb. Infect., 2020, vol. 22, iss. 2, pp. 72–73. doi: 10.1016/j.micinf.2020.02.00677. Tian X., Li C., Huang A., Xia S., Lu S., Shi Z., Lu L., Jiang S., Yang Z., Wu Y., Yinga T. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg. Microbes Infect., 2020, vol. 9, no. 1, pp. 382– 385. doi: 10.1080/22221751.2020.172906978. Traggiai E., Becker S., Subbarao K., Kolesnikova L., Uematsu Y., Gismondo M.R., Murphy B.R., Rappuoli R., Lanzavecchia A. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat. Med., 2004, vol. 10, no. 8, pp. 871–875. doi: 10.1038/nm108079. Velavan T.P., Meyer C.G. The COVID-19 epidemic. Trop. Med. Int. Health., 2020, vol. 25, no.3, pp. 278–280. doi: 10.1111/tmi.1338380. Vincent M.J., Bergeron E., Benjannet S., Erickson B.R., Rollin P.E., Ksiazek T.G., Seidah N.G., Nichol S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J., 2005, vol. 2: 69. doi: 10.1186/1743-422X-2-6981. Wang C., Li W., Drabek D., Okba N.M.A., van Haperen R., Osterhaus A.D.M.E., van Kuppeveld F.J.M., Haagmans B.L., Grosveld F., Bosch B.-J. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun., 2020, vol. 11: 2251. doi: 10.1101/2020.03.11.98795882. Wang G., Lu C.J., Trafford A.W., Tian X., Flores H.M., Maj P., Zhang K., Niu Y., Wang L., Du Y., Ji X., Xu Y., Wu L., Li D., Herring N., Paterson D., Huang C.L.-H., Zhang H., Lei M., Hao G. Mechanistic insights into ventricular arrhythmogenesis of hydroxychloroquine and azithromycin for the treatment of COVID-19. bioRxiv, 2020.05.21.108605. doi: 10.1101/2020.05.21.10860583. Wang H., Yang P., Liu K., Guo F., Zhang Y., Zhang G. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res., 2008, vol. 18, no. 2, pp. 290–301. doi: 10.1038/cr.2008.1584. Wang J., Hajizadeh N., Moore E.E., McIntyre R.C., Moore P.K., Veress L.A., Yaffe M.B., Moore H.B., Barrett C.D. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. J. Thromb. Haemost., 2020 Apr 8. doi: 10.1111/jth.1482885. Wang K., Chen W., Zhou Y.S., Lian J.Q., Zhang Z., Du P., Gong L., Zhang Y., Cui H.Y., Geng J.J., Wang B., Sun. X.-X., Wang C.F., Yang X., Lin P., Deng Y.Q., Wei D., Yang X.M., Zhu Y.M., Zhang K., Zheng Z.H., Miao J.L., Guo T., Si Y., Zhang J., Fu L., Wang Q.Y., Bian H., Zhu P., Chen Z.-N. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv, 2020.03.14.988345. doi: 10.1101/2020.03.14.98834586. Wong S.K., Li W., Moore M.J., Choe H., Farzan M.A. 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem., 2004, vol. 279, pp. 3197–201. doi: 10.1074/jbc.C30052020087. Wu P., Hao X., Lau E.H.Y., Wong J.Y., Leung K.S.M., Wu J.T., Cowling B.J., Leung G.M. Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveill., 2020, vol. 25, no. 3: 2000044. doi: 10.2807/156088. Xiong L., Edwards III C.K., Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int. J. Mol. Sci., 2014, vol. 15, no. 10, pp. 17411–17441. doi: 10.3390/ijms15101741189. Yang X., Yu Y., J. Xu, Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., Yu T., Wang Y., Pan S., Zou X., Yuan S., Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet, 2020,Feb 24. doi: 10.1016/S2213-2600(20)30079-590. Yao X., Ye F., Zhang M., Cui C., Huang B., Niu P., Liu X., Zhao L., Dong E., Song C., Zhan S., Lu R., Li H., Tan W., Liu D. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect. Dis., 2020: ciaa237. doi: 10.1093/cid/ciaa23791. Ye H., Wang X., Yuan X., Xiao G., Wang C., Deng T., Yuan Q., Xiao X. The epidemiology and clinical information about COVID-19. Eur. J. Clin. Microbiol. Infect. Dis., 2020, pp. 1–9. doi: 10.1007/s10096-020-03874-z92. Ye Q., Wang B., Mao J. The pathogenesis and treatment of the “Cytokine Storm” in COVID-19. J. Infect., 2020, vol. 80, iss. 6, pp. 607–613. doi: 10.1016/j.jinf.2020.03.03793. Yeh K.M., Chiueh T.S., Siu L.K., Lin J.C., Chan P.K.S., Peng M.Y., Wan H.L., Chen J.H., Hu B.S., Perng C.L., Lu J.J., Chang F.-Y. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J. Antimicrob. Chemother., 2005, vol. 56, no. 5, pp. 919–922. doi: 10.1093/jac/dki34694. Yin S., Huang M., Li D., Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J. Thromb. Thrombolysis, 2020, vol. 3, pp. 1–4. doi: 10.1007/s11239-020-02105-895. Yip M.S., Leung N.H.L., Cheung C.Y., Li P.H., Lee H.H.Y., Daëron M., Peiris J.S.M., Bruzzone R., Jaume M. Antibodydependent infection of human macrophages by severe acute respiratory syndrome coronavirus. Virol. J., 2014, vol. 11, p. 82. doi: 10.1186/1743-422X-11-8296. Yong C.Y., Ong H.K., Yeap S.K., Ho K.L., Tan W.S. Recent advances in the vaccine development against middle east respiratory syndrome-coronavirus. Front. Microbiol., 2019, vol. 10, p. 1781. doi: 10.3389/fmicb.2019.0178197. Zhai P., Ding Y., Wu X., Long J., Zhong Y., Lie Y., The epidemiology, diagnosis and treatment of COVID-19. Int. J. Antimicrob. Agents., 2020: 105955. doi: 10.1016/j.ijantimicag.2020.10595598. Zhang W., Zhao Y., Zhang F., Wang Q., Li T., Liu Z., Wang J., Qin Y., Zhang X., Yan X., Zeng X., Zhang S. The use of antiinflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the experience of clinical immunologists from China. Clin. Immunol., 2020: 108393. doi: 10.1016/j.clim.2020.10839399. Zhang Z.W., Xu X.C., Liu T., Yuan S. Mitochondrion-permeable antioxidants to treat ros-burst-mediated acute diseases. Oxid. Med. Cell. Longev., 2016, vol. 2016: 6859523. doi: 10.1155/2016/6859523n100. Zheng Z., Monteil V.M., Maurer-Stroh S., Yew C.W., Leong C., Mohd-Ismail N.K., Arularasu S.C., Chow V.T.K., Pin R.L.T., Mirazimi A., Hong W., Tan Y.-J. Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newlyemerged SARS-CoV-2. bioRxiv, 2020: 980037. doi: 10.1101/2020.03.06.980037101. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, vol. 395, no. 10229, pp. 1054–1062. doi: 10.1016/S0140-6736(20)30566-3102. Zhou G., Zhao Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. Int. J. Biol. Sci., 2020, vol. 16, no. 10, pp. 1718–1723. doi: 10.7150/ijbs.45123103. Zhou W.K., Wang A.L., Xia F., Xiao Y.N., Tang S.Y. Effects of media reporting on mitigating spread of COVID-19 in the early phase of the outbreak. Math. Biosci. Eng., 2020, vol. 17, no. 3, pp. 2693–2707. doi: 10.3934/mbe.2020147