mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-CTF-2095mimmun-2095Research ArticleОБЗОРЫREVIEWSЛекарства против COVID-19: от мифов к реалиям и надеждамCOVID-19 therapy: from myths to reality and hopesБозроваС. В.BozrovaS. V.

Бозрова Светална Викторовна – кандидат биологических наук, научный сотрудник, лаборатория молекулярных механизмов иммунитета

Москва

PhD (Biology), Research Associate, Laboratory of Molecular Mechanisms of Immunity

Moscow

svetaboz@yandex.ruhttps://orcid.org/0000-0003-3197-9779ДруцкаяМ. С.DrutskayaM. S.

Друцкая Марина Сергеевна – кандидат биологических наук, ведущий научный сотрудник, лаборатория молекулярных механизмов иммунитета

Москва

PhD (Biology), Leading Research Associate, Laboratory of Molecular Mechanisms of Immunity

Moscow

marinadru@gmail.comНедоспасовС. А.NedospasovS. A.

Недоспасов Сергей Артурович – доктор биологических наук, профессор, академик РАН, заведующий лабораторией молекулярных механизмов иммунитета ФГБУН «Институт молекулярной биологии имени В.А. Энгельгардта» Российской академии наук; заведующий кафедрой иммунологии биологического факультета ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова», Москва; научный руководитель направления «Иммунобиология и биомедицина», Научно-технологический университет «Сириус»

119991, Москва, ул. Вавилова, 32

Nedospasov Sergei А., PhD, MD (Biology), Professor, Full Member, Russian Academy of Sciences, Head, Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Head, Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Moscow; Head of the Section “Immunobiology and Biomedicine”, Sirius University of Science and Technology

119991, Moscow, Vavilova str., 32

 

sergei.nedospasov@gmail.comФГБУН «Институт молекулярной биологии имени В.А. Энгельгардта» Российской академии наукРоссияEngelhardt Institute of Molecular Biology, Russian Academy of SciencesRussian FederationФГБУН «Институт молекулярной биологии имени В.А. Энгельгардта» Российской академии наук; ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»; Научно-технологический университет «Сириус»РоссияEngelhardt Institute of Molecular Biology, Russian Academy of Sciences; Lomonosov Moscow State University; Sirius University of Science and TechnologyRussian Federation202027112020225827836Copyright © Бозрова С.В., Друцкая М.С., Недоспасов С.А., 20202020Бозрова С.В., Друцкая М.С., Недоспасов С.А.Bozrova S.V., Drutskaya M.S., Nedospasov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2095

Пандемия COVID-19, вызванная коронавирусом SARS-CoV-2, оказалась беспрецедентной для XXI века и уже затронула страны с суммарным населением в миллиарды человек. Число инфицированных уже превысило 30 миллионов человек, а число погибших перевалило за миллион. К сожалению, Россия пока входит в пятерку стран с наибольшим числом зараженных, хотя смертность от COVID-19 существенно ниже, чем во многих других странах. Поскольку вирус и вызываемый им патогенез имеют много новых и неожиданных черт, наукоемкие и специфичные именно для этого вируса лекарства и вакцины еще не созданы. В качестве мишеней будущих лекарств наиболее перспективны ферменты, необходимые для жизненного цикла именно этого вируса (такие как компоненты репликазного комплекса и вирусные протеазы). Форс-мажорные обстоятельства вынудили провести оценку целого ряда ранее разработанных лекарств, направленных против других РНК-содержащих вирусов, причем некоторые из них уже показали эффективность при клинических испытаниях против SARS-CoV-2. Не вызывает сомнения, что в скором времени будут найдены прототипы лекарств этого класса с более высокой специфичностью и эффективностью. Другую группу потенциальных лекарств представляют известные препараты, направленные против различных аспектов патогенеза, вызываемого SARS-CoV-2, в частности «цитокинового шторма» или коагулопатии. Следует подчеркнуть, что геном вируса кодирует около 10 дополнительных белков, часть из которых могут иметь отношение к необычным сторонам патогенеза при COVID-19. Проводимые фундаментальные исследования должны определить, какие из этих белков могут стать мишенями для специфической терапии. Наконец, тот факт, что в плазме крови многих переболевших находятся нейтрализующие антитела, которые можно использовать для профилактики и терапии COVID-19, во-первых, указывает на перспективность рекомбинантных нейтрализующих антител как лекарств и, во-вторых, подтверждает реальность создания профилактических вакцин. Этот мини-обзор посвящен обсуждению терапевтических подходов и статуса клинических испытаний с использованием препаратов, которые уже существовали до начала пандемии и исходно были разработаны против других инфекционных агентов или для лечения аутоиммунных патологий. Именно эти лекарства входят в сегодняшний арсенал средств и терапевтических протоколов, с помощью которых сейчас в разных странах пытаются справиться с эпидемией COVID-19.

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, is unprecedented for the 21st century and has already affected countries with a total population of billions of people. The number of infected has already surpassed 30 million people and the number of deaths has exceeded 1 million. Unfor-tunately, Russia is still one of the five countries with the largest number of infected people, although mortality from COVID-19 is significantly lower than in many other countries. Since the virus and the pathogenesis caused by it have a lot of new and unexpected features, high-tech and specific anti-viral drugs and vaccines have not yet been created. The most promising targets for future drug development are enzymes necessary for the life cycle of this particular virus (such as components of the replicase complex or viral proteases). Unexpected circumstances are pushing the evaluation of a number of previously developed and existing drugs directed toward other RNA viruses, some of which have already been shown effective in clinical trials against SARS-CoV-2. There is no doubt that soon prototypes of drugs of this class with higher specificity and effective-ness will be found. Another group of potential drugs are known drugs that are directed against various aspects of the pathogenesis caused by SARS-CoV-2, in particular, cytokine storm or coagulopathy. It should be emphasized that the genome of the virus encodes about 10 additional proteins, some of which may be related to unusual aspects of pathogenesis during COVID-19. Basic research should determine which of these proteins can be targets for specific therapy. Finally, the fact that neutralizing antibodies are found in the blood plasma of many patients and can be used for the prevention and treatment of COVID-19, indicates the potential of using recombinant neutralizing antibodies as drugs, and secondly, confirms the possibility of creating effective vaccines. This mini-review discusses therapeutic approaches and the status of clinical trials using drugs that already existed before the pandemic and were originally developed against other infectious agents or for the treatment of autoimmune pathologies. These drugs are part of today's arsenal in therapeutic protocols and are used in an attempt to cope with the COVID-19 epidemic in different countries.

противовирусная терапиякоронавирусSARS-CoV-2пандемияantiviral therapycoronavirusSARS-CoV-2pandemicРабота выполнена при поддержке гранта РФФИ № 20-04-60338ReferencesЛьвов Д.К., Альховский С.В. Истоки пандемии COVID-19: экология и генетика коронавирусов (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (подрод Sarbecovirus), MERS-CoV (подрод Merbecovirus) // Вопросы вирусологии, 2020. Т. 65, № 2. С. 62-70.Lvov D.K., Alkhovsky S.V. Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARSCoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus). Voprosy virusologii = Problems of Virology, 2020, Vol. 65, no. 2, pp. 62-70. (In Russ.)Aouba A., Baldolli A., Geffray L., Verdon R., Bergot E., Martin-Silva N., Justet A. Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Ann. Rheum. Dis., 2020, Vol. 79, no. 10, pp. 1381-1382.Aouba A., Baldolli A., Geffray L., Verdon R., Bergot E., Martin-Silva N., Justet A. Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Ann. Rheum. Dis., 2020, Vol. 79, no. 10, pp. 1381-1382.Asakura H., Ogawa H. Potential of heparin and nafamostat combination therapy for COVID-19. J. Thromb. Haemost., 2020, Vol. 18, no. 6, pp. 1521-1522.Asakura H., Ogawa H. Potential of heparin and nafamostat combination therapy for COVID-19. J. Thromb. Haemost., 2020, Vol. 18, no. 6, pp. 1521-1522.Barrett C.D., Moore H.B., Yaffe M.B., Moore E.E. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: а comment. J. Thromb. Haemost., 2020, Vol. 18, no. 8, pp. 2060-2063.Barrett C.D., Moore H.B., Yaffe M.B., Moore E.E. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: а comment. J. Thromb. Haemost., 2020, Vol. 18, no. 8, pp. 2060-2063.Bernal-Bello D., Jaenes-Barrios B., Morales-Ortega A., Ruiz-Giardin J.M., García-Bermúdez V., FrutosPérez B., Farfán-Sedano A.I., de Ancos-Aracil C., Bermejo F., García-Gil M., Zapatero-Gaviria A., San MartínLópez J.V. Imatinib might constitute a treatment option for lung involvement in COVID-19. Autoimmun. Rev., 2020, Vol. 19, no. 7, 102565. doi: 10.1016/j.autrev.2020.102565.Bernal-Bello D., Jaenes-Barrios B., Morales-Ortega A., Ruiz-Giardin J.M., García-Bermúdez V., FrutosPérez B., Farfán-Sedano A.I., de Ancos-Aracil C., Bermejo F., García-Gil M., Zapatero-Gaviria A., San MartínLópez J.V. Imatinib might constitute a treatment option for lung involvement in COVID-19. Autoimmun. Rev., 2020, Vol. 19, no. 7, 102565. doi: 10.1016/j.autrev.2020.102565.Cantini F., Niccoli L., Nannini C., Matarrese D., Di Natale M.E., Lotti P., Aquilini D., Landini G., Cimolato B., Di Pietro M.A., Trezzi M., Stobbione P., Frausini G., Navarra A., Nicastri E., Sotgiu G., Goletti D. Retrospective, multicenter study on the impact of baricitinib in COVID-19 moderate pneumonia. J. Infect., 2020. doi: 10.1016/j.jinf.2020.06.052.Cantini F., Niccoli L., Nannini C., Matarrese D., Di Natale M.E., Lotti P., Aquilini D., Landini G., Cimolato B., Di Pietro M.A., Trezzi M., Stobbione P., Frausini G., Navarra A., Nicastri E., Sotgiu G., Goletti D. Retrospective, multicenter study on the impact of baricitinib in COVID-19 moderate pneumonia. J. Infect., 2020. doi: 10.1016/j.jinf.2020.06.052.Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., Ruan L., Song B., Cai Y., Wei M., Li X., Xia J., Chen N., Xiang J., Yu T., Bai T., Xie X., Zhang L., Li C., Yuan Y., Chen H., Li H., Huang H., Tu S., Gong F., Liu Y., Wei Y., Dong C., Zhou F., Gu X., Xu J., Liu Z., Zhang Y., Li H., Shang L., Wang K., Li K., Zhou X., Dong X., Qu Z., Lu S., Hu X., Ruan S., Luo S., Wu J., Peng L., Cheng F., Pan L., Zou J., Jia C., Wang J., Liu X., Wang S., Wu X., Ge Q., He J., Zhan H., Qiu F., Guo L., Huang C., Jaki T., Hayden F.G., Horby P.W., Zhang D., Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. New Engl. J. Med., 2020, Vol. 382, no. 19, pp. 1787-1799.Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., Ruan L., Song B., Cai Y., Wei M., Li X., Xia J., Chen N., Xiang J., Yu T., Bai T., Xie X., Zhang L., Li C., Yuan Y., Chen H., Li H., Huang H., Tu S., Gong F., Liu Y., Wei Y., Dong C., Zhou F., Gu X., Xu J., Liu Z., Zhang Y., Li H., Shang L., Wang K., Li K., Zhou X., Dong X., Qu Z., Lu S., Hu X., Ruan S., Luo S., Wu J., Peng L., Cheng F., Pan L., Zou J., Jia C., Wang J., Liu X., Wang S., Wu X., Ge Q., He J., Zhan H., Qiu F., Guo L., Huang C., Jaki T., Hayden F.G., Horby P.W., Zhang D., Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. New Engl. J. Med., 2020, Vol. 382, no. 19, pp. 1787-1799.Cao Y., Wei J., Zou L., Jiang T., Wang G., Chen L., Huang L., Meng F., Huang L., Wang N., Zhou X., Luo H., Mao Z., Chen X., Xie J., Liu J., Cheng H., Zhao J., Huang G., Wang W., Zhou J. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): а multicenter, single-blind, randomized controlled trial. J. Allergy Clin. Immunol., 2020, Vol. 146, no. 1, pp. 137-146.e3Cao Y., Wei J., Zou L., Jiang T., Wang G., Chen L., Huang L., Meng F., Huang L., Wang N., Zhou X., Luo H., Mao Z., Chen X., Xie J., Liu J., Cheng H., Zhao J., Huang G., Wang W., Zhou J. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): а multicenter, single-blind, randomized controlled trial. J. Allergy Clin. Immunol., 2020, Vol. 146, no. 1, pp. 137-146.e3Chakraborty C., Sharma A.R., Bhattacharya M., Sharma G., Lee S., Agoramoorthy G. COVID-19: сonsider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS-CoV-2 infected patients. J. Med. Virol., 2020. doi: 10.1002/jmv.26078.Chakraborty C., Sharma A.R., Bhattacharya M., Sharma G., Lee S., Agoramoorthy G. COVID-19: сonsider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS-CoV-2 infected patients. J. Med. Virol., 2020. doi: 10.1002/jmv.26078.Curtin N., Bányai K., Thaventhiran J., le Quesne J., Helyes Z., Bai P. Repositioning PARP inhibitors for SARS-CoV-2 infection (COVID-19); a new multi-pronged therapy for ARDS? Br. J. Pharmacol., 2020, Vol. 177, no. 16, pp. 3635-3645.Curtin N., Bányai K., Thaventhiran J., le Quesne J., Helyes Z., Bai P. Repositioning PARP inhibitors for SARS-CoV-2 infection (COVID-19); a new multi-pronged therapy for ARDS? Br. J. Pharmacol., 2020, Vol. 177, no. 16, pp. 3635-3645.Du Y.X., Chen X.P. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. Clin. Pharmacol. Ther., 2020, Vol. 108, no. 2, pp. 242-247.Du Y.X., Chen X.P. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. Clin. Pharmacol. Ther., 2020, Vol. 108, no. 2, pp. 242-247.Elfiky A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci., 2020, Vol. 253, 117592. doi: 10.1016/j.lfs.2020.117592.Elfiky A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci., 2020, Vol. 253, 117592. doi: 10.1016/j.lfs.2020.117592.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, 2020, Vol. 395, no. 10234, pp. 1407-1409.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, 2020, Vol. 395, no. 10234, pp. 1407-1409.Goldstein L.D., Chen Y.J.J., Wu J., Chaudhuri S., Hsiao Y.C., Schneider K., Hoi K.H., Lin Z., Guerrero S., Jaiswal B.S., Stinson J., Antony A., Pahuja K.B., Seshasayee D., Modrusan Z., Hötzel I., Seshagiri S. Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies. Commun. Biol., 2019, Vol. 2, 304. doi: 10.1038/s42003-019-0551-y.Goldstein L.D., Chen Y.J.J., Wu J., Chaudhuri S., Hsiao Y.C., Schneider K., Hoi K.H., Lin Z., Guerrero S., Jaiswal B.S., Stinson J., Antony A., Pahuja K.B., Seshasayee D., Modrusan Z., Hötzel I., Seshagiri S. Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies. Commun. Biol., 2019, Vol. 2, 304. doi: 10.1038/s42003-019-0551-y.Gordon C.J., Tchesnokov E.P., Feng J.Y., Porter D.P., Götte M. The antiviral compound remdesivir potently inhibits RNAdependent RNA polymerase from Middle East respiratory syndrome coronavirus. J. Biol. Chem., 2020, Vol. 295, no. 15, pp. 4773-4779.Gordon C.J., Tchesnokov E.P., Feng J.Y., Porter D.P., Götte M. The antiviral compound remdesivir potently inhibits RNAdependent RNA polymerase from Middle East respiratory syndrome coronavirus. J. Biol. Chem., 2020, Vol. 295, no. 15, pp. 4773-4779.Hermans C., Lambert C. Impact of the COVID-19 pandemic on therapeutic choices in ThrombosisHemostasis. J. Thromb. Haemost., 2020, Vol. 18, no. 7, pp. 1794-1795.Hermans C., Lambert C. Impact of the COVID-19 pandemic on therapeutic choices in ThrombosisHemostasis. J. Thromb. Haemost., 2020, Vol. 18, no. 7, pp. 1794-1795.Horby P., Lim W.S., Emberson J., Mafham M., Bell J., Linsell L., Staplin N., Brightling C., Ustianowski A., Elmahi E., Prudon B., Green C., Felton T., Chadwick D., Rege K., Fegan C., Chappell L.C., Faust S.N., Jaki T., Jeffery K., Montgomery A., Rowan K., Juszczak E., Baillie J.K., Haynes R., Landray M.J., Group R.C. Effect of Dexamethasone in hospitalized patients with COVID-19: preliminary report. N. Engl. J. Med., 2020. doi: 10.1056/NEJMoa2021436.Horby P., Lim W.S., Emberson J., Mafham M., Bell J., Linsell L., Staplin N., Brightling C., Ustianowski A., Elmahi E., Prudon B., Green C., Felton T., Chadwick D., Rege K., Fegan C., Chappell L.C., Faust S.N., Jaki T., Jeffery K., Montgomery A., Rowan K., Juszczak E., Baillie J.K., Haynes R., Landray M.J., Group R.C. Effect of Dexamethasone in hospitalized patients with COVID-19: preliminary report. N. Engl. J. Med., 2020. doi: 10.1056/NEJMoa2021436.Khalili J.S., Zhu H., Mak N.S.A., Yan Y., Zhu Y. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID-19. J. Med. Virol., 2020, Vol. 92, no. 7, pp. 740-746.Khalili J.S., Zhu H., Mak N.S.A., Yan Y., Zhu Y. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID-19. J. Med. Virol., 2020, Vol. 92, no. 7, pp. 740-746.Meyerowitz E.A., Vannier A.G.L., Friesen M.G.N., Schoenfeld S., Gelfand J.A., Callahan M.V., Kim A.Y., Reeves P.M., Poznansky M.C. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J., 2020, Vol. 34, no. 5, pp. 6027-6037.Meyerowitz E.A., Vannier A.G.L., Friesen M.G.N., Schoenfeld S., Gelfand J.A., Callahan M.V., Kim A.Y., Reeves P.M., Poznansky M.C. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J., 2020, Vol. 34, no. 5, pp. 6027-6037.Ramanathan A., Robb G.B., Chan S.H. mRNA capping: biological functions and applications. Nucleic Acids Res., 2016, Vol. 44, no. 16, pp. 7511-7526.Ramanathan A., Robb G.B., Chan S.H. mRNA capping: biological functions and applications. Nucleic Acids Res., 2016, Vol. 44, no. 16, pp. 7511-7526.Rojas M., Rodríguez Y., Monsalve D.M., Acosta-Ampudia Y., Camacho B., Gallo J.E., Rojas-Villarraga A., Ramírez-Santana C., Díaz-Coronado J.C., Manrique R., Mantilla R.D., Shoenfeld Y., Anaya J.M. Convalescent plasma in Covid-19: possible mechanisms of action. Autoimmun. Rev., 2020, Vol. 19, no. 7, 102554. doi: 10.1016/j.autrev.2020.102554.Rojas M., Rodríguez Y., Monsalve D.M., Acosta-Ampudia Y., Camacho B., Gallo J.E., Rojas-Villarraga A., Ramírez-Santana C., Díaz-Coronado J.C., Manrique R., Mantilla R.D., Shoenfeld Y., Anaya J.M. Convalescent plasma in Covid-19: possible mechanisms of action. Autoimmun. Rev., 2020, Vol. 19, no. 7, 102554. doi: 10.1016/j.autrev.2020.102554.Rothlin R.P., Vetulli H.M., Duarte M., Pelorosso F.G. Telmisartan as tentative angiotensin receptor blocker therapeutic for COVID-19. Drug Dev. Res., 2020. doi: 10.1002/ddr.21679.Rothlin R.P., Vetulli H.M., Duarte M., Pelorosso F.G. Telmisartan as tentative angiotensin receptor blocker therapeutic for COVID-19. Drug Dev. Res., 2020. doi: 10.1002/ddr.21679.Saavedra J.M. Angiotensin receptor blockers and COVID-19. Pharmacol. Res., 2020, Vol. 156, 104832. doi: 10.1016/j.phrs.2020.104832.Saavedra J.M. Angiotensin receptor blockers and COVID-19. Pharmacol. Res., 2020, Vol. 156, 104832. doi: 10.1016/j.phrs.2020.104832.Sallard E., Lescure F.X., Yazdanpanah Y., Mentre F., Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res., 2020, Vol. 178, 104791. doi: 10.1016/j.antiviral.2020.104791.Sallard E., Lescure F.X., Yazdanpanah Y., Mentre F., Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res., 2020, Vol. 178, 104791. doi: 10.1016/j.antiviral.2020.104791.Setliff I., Shiakolas A.R., Pilewski K.A., Murji A.A., Mapengo R.E., Janowska K., Richardson S., Oosthuysen C., Raju N., Ronsard L., Kanekiyo M., Qin J.S., Kramer K.J., Greenplate A.R., McDonnell W.J., Graham B.S., Connors M., Lingwood D., Acharya P., Morris L., Georgiev I.S. High-throughput mapping of B cell receptor sequences to antigen specificity. Cell, 2019, Vol. 179, no. 7, pp. 1636-1646.e15.Setliff I., Shiakolas A.R., Pilewski K.A., Murji A.A., Mapengo R.E., Janowska K., Richardson S., Oosthuysen C., Raju N., Ronsard L., Kanekiyo M., Qin J.S., Kramer K.J., Greenplate A.R., McDonnell W.J., Graham B.S., Connors M., Lingwood D., Acharya P., Morris L., Georgiev I.S. High-throughput mapping of B cell receptor sequences to antigen specificity. Cell, 2019, Vol. 179, no. 7, pp. 1636-1646.e15.Takeda A., Tuazon C.U., Ennis F.A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science, 1988, Vol. 242, no. 4878, pp. 580-583.Takeda A., Tuazon C.U., Ennis F.A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science, 1988, Vol. 242, no. 4878, pp. 580-583.Tamura M., Webster R.G., Ennis F.A. Antibodies to HA and NA augment uptake of influenza A viruses into cells via Fc receptor entry. Virology, 1991, Vol. 182, no. 1, pp. 211-219.Tamura M., Webster R.G., Ennis F.A. Antibodies to HA and NA augment uptake of influenza A viruses into cells via Fc receptor entry. Virology, 1991, Vol. 182, no. 1, pp. 211-219.Testa S., Paoletti O., Giorgi-Pierfranceschi M., Pan A. Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients. Intern. Emerg. Med., 2020, pp. 1-3. doi: 10.1007/s11739-020-02331-1.Testa S., Paoletti O., Giorgi-Pierfranceschi M., Pan A. Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients. Intern. Emerg. Med., 2020, pp. 1-3. doi: 10.1007/s11739-020-02331-1.Thachil J., Tang N., Gando S., Falanga A., Cattaneo M., Levi M., Clark C., Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J. Thromb. Haemost., 2020, Vol. 18, no. 5, pp. 1023-1026.Thachil J., Tang N., Gando S., Falanga A., Cattaneo M., Levi M., Clark C., Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J. Thromb. Haemost., 2020, Vol. 18, no. 5, pp. 1023-1026.Tomasoni D., Italia L., Adamo M., Inciardi R.M., Lombardi C.M., Solomon S.D., Metra M. COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease. Eur. J. Heart Fail., 2020, Vol. 22, no. 6, pp. 957-966.Tomasoni D., Italia L., Adamo M., Inciardi R.M., Lombardi C.M., Solomon S.D., Metra M. COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease. Eur. J. Heart Fail., 2020, Vol. 22, no. 6, pp. 957-966.Uno Y. Camostat mesilate therapy for COVID-19. Intern. Emerg. Med., 2020, pp. 1-2. doi: 10.1007/s11739-020-02345-9.Uno Y. Camostat mesilate therapy for COVID-19. Intern. Emerg. Med., 2020, pp. 1-2. doi: 10.1007/s11739-020-02345-9.Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, Vol. 323, no. 11, pp. 1061-1069.Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, Vol. 323, no. 11, pp. 1061-1069.Yamamoto M., Matsuyama S., Li X., Takeda M., Kawaguchi Y., Inoue J.I., Matsuda Z. Identification of nafamostat as a potent inhibitor of middle east respiratory syndrome Coronavirus s protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob. Agents Chemother., 2016, Vol. 60, no. 11, pp. 6532-6539Yamamoto M., Matsuyama S., Li X., Takeda M., Kawaguchi Y., Inoue J.I., Matsuda Z. Identification of nafamostat as a potent inhibitor of middle east respiratory syndrome Coronavirus s protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob. Agents Chemother., 2016, Vol. 60, no. 11, pp. 6532-6539Yin W., Mao C., Luan X., Shen D.-D., Shen Q., Su H., Wang X., Zhou F., Zhao W., Gao M., Chang S., Xie Y.-C., Tian G., Jiang H.-W., Tao S.-C., Shen J., Jiang Y., Jiang H., Xu Y., Zhang S., Zhang Y., Xu H.E. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, Vol. 368, no. 6498, pp. 1499-1504.Yin W., Mao C., Luan X., Shen D.-D., Shen Q., Su H., Wang X., Zhou F., Zhao W., Gao M., Chang S., Xie Y.-C., Tian G., Jiang H.-W., Tao S.-C., Shen J., Jiang Y., Jiang H., Xu Y., Zhang S., Zhang Y., Xu H.E. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, Vol. 368, no. 6498, pp. 1499-1504.Zhang Z., Wang S., Tu X., Peng X., Huang Y., Wang L., Ju W., Rao J., Li X., Zhu D., Sun H., Chen H. A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19. J. Med. Virol., 2020. doi: 10.1002/jmv.26141.Zhang Z., Wang S., Tu X., Peng X., Huang Y., Wang L., Ju W., Rao J., Li X., Zhu D., Sun H., Chen H. A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19. J. Med. Virol., 2020. doi: 10.1002/jmv.26141.Zhang C., Wu Z., Li J.W., Zhao H., Wang G.Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int. J. Antimicrob. Agents, 2020, Vol. 55, no. 5, 105954. doi: 10.1016/j.ijantimicag.2020.105954.Zhang C., Wu Z., Li J.W., Zhao H., Wang G.Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int. J. Antimicrob. Agents, 2020, Vol. 55, no. 5, 105954. doi: 10.1016/j.ijantimicag.2020.105954.Zhang J.M., An J. Cytokines, inflammation, and pain. Int. Anesthesiol. Clin., 2007, Vol. 45, no. 2, pp. 27-37.Zhang J.M., An J. Cytokines, inflammation, and pain. Int. Anesthesiol. Clin., 2007, Vol. 45, no. 2, pp. 27-37.Zhang W.F., Stephen P., Thériault J.F., Wang R., Lin S.X. Novel Coronavirus polymerase and nucleotidyltransferase structures: potential to target new outbreaks. J. Phys. Chem. Lett., 2020, Vol. 11, no. 11, pp. 4430-4435.Zhang W.F., Stephen P., Thériault J.F., Wang R., Lin S.X. Novel Coronavirus polymerase and nucleotidyltransferase structures: potential to target new outbreaks. J. Phys. Chem. Lett., 2020, Vol. 11, no. 11, pp. 4430-4435.

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