Strategies for search of pharmacological drugs against SARS-CoV-2 on the base of studying the structural-genetic features of coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2

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Abstract

A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. Also the basic molecular mechanisms of an atypical pneumonia and molecular targets SARS-CoV-2 that allows to allocate 8 basic directions of search of pharmacological agents for struggle with SARS-CoV-2 are discussed. Mathematical methods of search of perspective preparations for struggle with COVID-19 are in detail discussed. The pathophysiological mechanisms of an infection inducing a lymphopenia or cytokine storm that allows to allocate a special direction of search of pharmacological preparations for struggle against new coronaviruse SARS-CoV-2 are discussed.

About the authors

Vladimir I. Vashchenko

S.M. Kirov Military Medical Academy

Author for correspondence.
Email: vladimir-vaschenko@yandex.ru

Dr. Biol. Sci., Head, Department of Biochemistry, Centre of Blood and Tissues

Russian Federation, Saint Petersburg

Vladimir N. Vilyaninov

S.M. Kirov Military Medical Academy

Email: vilyaninov@mail.ru

PhD, Chief, Centre of Blood and Tissues

Russian Federation, Saint Petersburg

Petr D. Shabanov

S.M. Kirov Military Medical Academy

Email: pdshabanov@mail.ru

Dr. Med. Sci., Professor and Head, Department of Pharmacology

Russian Federation, Saint Petersburg

References

  1. Авифавир. Лекарственный препарат. ГРЛС: № ЛП- 006225-290520. 2020. [Avifavir. Lekarstvennyy preparat. GRLS: No. LP-006225-290520, 2020. (In Russ.)]
  2. Арбидол. Лекарственный препарат. ГРЛС: № Р N003610/01. 10.05.2007. [Arbidol. Lekarstvennyy preparat. GRLS: No. Р N003610/01. 10.05.2007. (In Russ.)]
  3. Арепливир. Лекарственный препарат. ГРЛС: № ЛП-006288-2306. 2020. [Areplivir. Lekarstvennyy preparat. GRLS: No. LP-006288-2306. 2020. (In Russ.)]
  4. Бугреев Д.В., Невинский Г.А. Структура и механизм действия ДНК-топоизомераз IА-типа // Успехи биологической химии. – 2009. – Т. 49. – С. 129–158. [Bugreev DV, Nevinskiy GA. Struktura i mekhanizm deystviya DNK-topoizomeraz IA-tipa. Uspekhi biologicheskoy khimii. 2009;49:129-158. (In Russ.)]
  5. Ващенко В.И., Вильянинов В.Н., Шабанов П.Д. Противомикробное и противовирусное действие дефенсинов человека: патогенетическое значение и перспективы применения в лекарственной терапии // Обзоры по клинической фармакологии и лекарственной терапии. – 2016. – Т. 14. – № 2. – С. 3–37. [Vaschenko VI, Vil’yaninov VN, Shabanov PD. Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy. Reviews on Clinical Pharmacology and Drug Therapy. 2016;14(2):3-37. (In Russ.)]. https://doi.org/10.17816/RCF1423-37.
  6. Жирнов О.П., Бокова Н.О., Исаева Е.И., и др. Патогенетическое лечение гриппа с помощью аэрозольной формы апротинина, ингибитора протеаз // Биопрепараты. Профилактика, диагностика, лечение. – 2015. – № 4. – C. 59–64. [Zhirnov OP, Bokova NO, Isaeva EI, et al. Pathogenetic treatment of influenza patients with aerosolized form of aprotinin, a protease inhibitor. Biopreparaty. Profilaktika, diagnostika, lechenie. 2015;(4):59-64. (In Russ.)]
  7. Жирнов О.П. Молекулярные мишени в химиотерапии коронавирусной инфекции // Биохимия. – 2020. – Т. 85. – № 5. – С. 611–619. [Zhirnov OP. Molecular targets in the chemotherapy of coronavirus infection. Biokhimiia. 2020;85(5):611-619. (In Russ.)]
  8. Кокряков В.Н. Очерки о врожденном иммунитете. – СПб.: Наука, 2006. – 261 c. [Kokryakov VN. Ocherki o vrozhdennom immunitete. Saint Petersburg: Nauka; 2006. 261 p. (In Russ.)]
  9. Коронавир. Лекарственный препарат. ГРЛС: № ЛП-006323–06.06.2020. [Koronavir. Lekarstvennyy preparat. GRLS: № LP-006323-06.06.2020. (In Russ.)]
  10. Кулагина М.Г., Венгеров Ю.Я. Коронавирусная инфекция. В кн.: Инфекционные болезни: национальное руководство / Под ред. Н.Д. Ющука, Ю.Я. Венгерова. – М., 2018. – 756–768. [Kulagina MG, Vengerov YuYa. Koronavirusnaya infektsiya. In: Infektsionnye bolezni: natsional’noe rukovodstvo. Ed. by N.D. Yushchuk, Yu.Ya. Vengerov. Мoscow; 2018. p. 759-768. (In Russ.)]
  11. Маджидов Т.И., Куракин Г.Ф. Компьютерные технологии против коронавируса: первые результаты // Природа. – 2020. – № 3. – С. 3–15. [Madzhidov TI, Kurakin GF. Computer technologies against coronavirus: first results. Priroda. 2020;(3):3-15. (In Russ.)]. https://doi.org/10.7868/S0032874X20030011.
  12. Марахонов А.В., Баранова А.В., Скоблов М.Ю. РНК-интерференция: Фундаментальные и прикладные аспекты // Медицинская генетика. – 2008. – Т. 7. – № 10. – C. 44–56. [Marakhonov AV, Baranova AV, Skoblov MYu. RNA interference: fundamentals and application. Medical genetics. 2008;7(10):44-56. (In Russ.)]
  13. Министерство здравоохранения РФ. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Временные методические рекомендации МЗ РФ. Версия 9 (26.10.2020). – М.: Минздрав РФ, 2020. – 236 с. [Ministry of health of the Russian Federation. Profilaktika, diagnostika i lecheniye novoy koronavirusnoy infektsii (COVID-19). Vremennyye metodicheskiye rekomendatsii Minzdrava Rossii. Versiya 9 (26.10.2020). Moscow: Ministry of Health of the Russian Federation, 2020. 236 р. (In Russ.)]
  14. Руководство по профилактике и лечению новой коронавирусной инфекции COVID-19. Первая академическая клиника Университетской школы медицины провинции Чжецзян. Составлено на основе клинической практики. – M.: МИА «Россия сегодня», 2020. – 89 c. [Rukovodstvo po profilaktike i lecheniyu novoy koronavirusnoy infektsii COVID-19. Pervaya akademicheskaya klinika Universitetskoy shkoly meditsiny provintsii Chzhetszyan. Sostavleno na osnove klinicheskoy praktiki. Mоscow: MIA “Rossiya segodnya”; 2020. 89 p. (In Russ.)]
  15. Харченко Е.П. Коронавирус SARS-Cov-2: особенности структурных белков, контагиозность и возможные иммунные коллизии // Эпидемиология и вакцинопрофилактика. – 2020. – Т. 19. – № 2. – C. 13–30. [Kharchenko EP. The Coronavirus SARS-Cov-2: the Characteristics of Structural Proteins, Contagiousness, and Possible Immune Collisions. Epidemiology and Vaccinal Prevention. 2020;19(2):13-30. (In Russ.)]. https://doi.org/10.31631/2073-3046-2020-20-2-13-30.
  16. Abdel-Moneim AS. Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations. Arch Virol. 2014;159(7):1575-1584. https://doi.org/10.1007/s00705-014-1995-5.
  17. Adhikari SP, Meng S, Wu YJ, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty. 2020;9(1):29. https://doi.org/10.1186/s40249-020-00646-x.
  18. Ahmadpour D, Ahmadpoor P. How COVID-19 overcomes the battle? An approach to virus structure. Iran J Kidney Dis. 2020;14(3):167-172.
  19. Alexpandi R, De Mesquita JF, Pandian SK, Ravi AV. Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis. Front Microbiol. 2020;11:1796. https://doi.org/10.3389/fmicb. 2020.01796.
  20. Andersen KG, Rambaut A, Lipkin WI, et al. The proximal origin of SARS-CoV-2. Nat Med. 2020;26(4):450-452. https://doi.org/10.1038/s41591-020-0820-9.
  21. Angeletti S, Benvenuto D, Bianchi M, et al. COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis. J Med Virol. 2020;92(6):584-588. https://doi.org/10.1002/jmv.25719.
  22. Arabi YM, Hajeer AH, Luke T, et al. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016;22(9): 1554-1561. https://doi.org/10.3201/eid2209.151164.
  23. Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens. 2020;9(3). https://doi.org/10.3390/pathogens9030186.
  24. Arun KG, Sharanya CS, Abhithaj J, et al. Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target. J Biomol Struct Dyn. 2020:1-12. https://doi.org/10.1080/07391102.2020.1779819.
  25. Baldelli S, Corbellino M, Clementi E, et al. Lopinavir/ritonavir in COVID-19 patients: maybe yes, but at what dose? J Antimicrob Chemother. 2020;75(9):2704-2706. https://doi.org/10.1093/jac/dkaa190.
  26. Barlow A, Landolf KM, Barlow B, et al. Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019. Pharmacotherapy. 2020;40(5):416-437. https://doi.org/10.1002/phar.2398.
  27. Beck BR, Shin B, Choi Y, et al. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J. 2020;18: 784-790. https://doi.org/10.1016/j.csbj.2020.03.025.
  28. Beigel JH, Voell J, Kumar P, et al. Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study. Lancet Infect Dis. 2018;18(4):410-418. https://doi.org/10.1016/s1473-3099(18)30002-1.
  29. Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012;4(6):1011-1033. https://doi.org/10.3390/v4061011.
  30. Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol. 2006;13(8):751-752. https://doi.org/10.1038/nsmb1123.
  31. Bimonte S, Crispo A, Amore A, et al. Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research. In Vivo. 2020;34(3 Suppl): 1597-1602. https://doi.org/10.21873/invivo.11949.
  32. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. https://doi.org/10.1056/NEJMoa2001282.
  33. Carter JB, Saunders VA. Virology: Principles and Applications. John Wiley and Sons Ltd; 2007. 383 p.
  34. Cavasotto CN, Di Filippo JI. In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Consensus Ranking. Mol Inform. 2020. https://doi.org/10.1002/minf.202000115.
  35. Cattaneo D, Cattaneo D, Gervasoni C, et al. Does lopinavir really inhibit SARS-CoV-2? Pharmacol Res. 2020;158:104898. https://doi.org/10.1016/j.phrs.2020. 104898.
  36. Ceraolo C, Giorgi FM. Genomic variance of the 2019-nCoV coronavirus. J Med Virol. 2020;92(5):522-528. https://doi.org/10.1002/jmv.25700.
  37. Chan JF, Yao Y, Yeung ML, et al. Treatment with Lopinavir/Ritonavir or Interferon-beta1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis. 2015;212(12): 1904-1913. https://doi.org/10.1093/infdis/jiv392.
  38. Сhakraborty AK. Coronavirus Nsp2 protein homologies to the bacterial DNA Topoisomerase I and IV suggest Nsp2 protein is a unique RNA Topoisomerase with novel target for drug and vaccine development. Virol Mycol. 2020;9(1):185. https://doi.org/10.35248/2161-0517.20.09.185.
  39. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529-539. https://doi.org/10.1007/s00281-017-0629-x.
  40. Chatterjee S, Maity A, Chowdhury S, et al. In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme. J Biomol Struct Dyn. 2020:1-14. https://doi.org/10.1080/07391102.2020.1787228.
  41. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020;20(4):398-400. https://doi.org/10.1016/s1473-3099(20)30141-9.
  42. Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-423. https://doi.org/10.1002/jmv.25681.
  43. Chen Y, Shan K, Qian W. Asians and Other Races Express Similar Levels of and Share the Same Genetic Polymorphisms of the SARS-CoV-2 Cell-Entry Receptor. Preprints.org. 2020. https://doi.org/10.20944/preprints202002.0258.v1.
  44. Chen YW, Yiu C-PB, Wong K-Y. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Research. 2020;9:129. https://doi.org/10.12688/f1000research. 22457.2.
  45. Cherian SS, Agrawal M, Basu A, et al. Perspectives for repurposing drugs for the coronavirus disease 2019. Indian J Med Res. 2020;151(2 & 3):160-171. https://doi.org/10.4103/ijmr.IJMR_585_20.
  46. Cho JB, Lee JM, Ahn HC, Jeong YJ. Identification of a Novel Small Molecule Inhibitor Against SARS Coronavirus Helicase. J Microbiol Biotechnol. 2015;25(12):2007-2010. https://doi.org/10.4014/jmb.1507.07078.
  47. Chu H, Zhou J, Wong BH, et al. Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways. J Infect Dis. 2016;213(6):904-914. https://doi.org/10.1093/infdis/jiv380.
  48. Cinatl J, Morgenstern B, Bauer G, et al. Treatment of SARS with human interferons. Lancet. 2003;362(9380):293-294. https://doi.org/10.1016/s0140-6736(03)13973-6.
  49. Cornelissen LA, Wierda CM, van der Meer FJ, et al. Hemagglutinin-esterase, a novel structural protein of torovirus. J Virol. 1997;71(7):5277-5286. https://doi.org/10.1128/jvi.71.7.5277-5286.1997.
  50. Costanzo M, De Giglio MAR, Roviello GN. SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and other Drugs for the Treatment of the New Coronavirus. Curr Med Chem. 2020;27(27):4536-4541. https://doi.org/10.2174/0929867327666200416131117.
  51. Coutard B, Valle C, de Lamballerie X, et al. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 2020;176:104742. https://doi.org/10.1016/j.antiviral.2020.104742.
  52. Cui L, Wang H, Ji Y, et al. The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells. J Virol. 2015;89(17):9029-9043. https://doi.org/10.1128/JVI.01331-15.
  53. Cui S, Hao W. Deducing the Crystal Structure of MERS-CoV Helicase. Methods Mol Biol. 2020;2099:69-85. https://doi.org/10.1007/978-1-0716-0211-9_6.
  54. Dai W, Zhang B, Jiang XM, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020;368(6497):1331-1335. https://doi.org/10.1126/science.abb4489.
  55. Drozdzal S, Rosik J, Lechowicz K, et al. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy. Drug Resist Updat. 2020;53:100719. https://doi.org/10.1016/j.drup.2020.100719.
  56. de Groot RJ, Baker SC, Baric R, et al. Family Coronaviridae. In: Virus Taxonomy. Ninth Report of the International Committee on Taxonomy of Viruses. Ed. by A.M.Q. King, Adams M.J., Carstens E.B., Lefkowitz E.J. Elsevier; 2012. p. 806-828.
  57. Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018;153:85-94. https://doi.org/10.1016/j.antiviral.2018.03.003.
  58. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1): 58-60. https://doi.org/10.5582/ddt.2020.01012.
  59. Donmez I, Patel SS. Mechanisms of a ring shaped helicase. Nucleic Acids Res. 2006;34(15):4216-4224. https://doi.org/10.1093/nar/gkl508.
  60. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA. 2020;117(17):9490-9496. https://doi.org/10.1073/pnas.2004168117.
  61. Du YX, Chen XP. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin Pharmacol Ther. 2020;108(2):242-247. https://doi.org/10. 1002/cpt.1844.
  62. Eastman RT, Roth JS, Brimacombe KR, et al. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020;6(5):672-683. https://doi.org/10.1021/acscentsci.0c00489.
  63. Eggleston M. Clinical review of ribavirin. Infect Control. 1987;8(5):215-218. https://doi.org/10.1017/s0195941700065978.
  64. Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020;253:117592. https://doi.org/10.1016/j.lfs.2020.117592.
  65. Elmezayen AD, Al-Obaidi A, Sahin AT, Yelekci K. Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. J Biomol Struct Dyn. 2020:1-13. https://doi.org/10.1080/07391102.2020.1758791.
  66. Fan H, Ooi A, Tan YW, et al. The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties. Structure. 2005;13(12):1859-1868. https://doi.org/10.1016/j.str.2005.08.021.
  67. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1-23. https://doi.org/10.1007/978-1-4939-2438-7_1.
  68. Chen Y, Feng Z, Diao B, et al. The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes. medRxiv. 2020. https://doi.org/10.1101/2020.03.27.20045427.
  69. Fung TS, Liu DX. Human Coronavirus: Host-Pathogen Interaction. Ann Rev Microbiol. 2019;73(1):529-557. https://doi.org/10.1146/annurev-micro-020518-115759.
  70. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-73. https://doi.org/10.5582/bst.2020.01047.
  71. Gao K, Nguyen DD, Chen J, et al. Repositioning of 8565 Existing Drugs for COVID-19. J Phys Chem Lett. 2020;11(13):5373-5382. https://doi.org/10.1021/acs.jpclett.0c01579.
  72. Gilbert BE, Knight V. Biochemistry and clinical applications of ribavirin. Antimicrob Agents Chemother. 1986;30(2): 201-205. https://doi.org/10.1128/aac.30.2.201.
  73. Goldsmith CS, Tatti KM, Ksiazek TG, et al. Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis. 2004;10(2):320-326. https://doi.org/10.3201/eid1002.030913.
  74. Goo J, Jeong Y, Park YS, et al. Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein. Virus Res. 2020;278:197863. https://doi.org/10.1016/j.virusres.2020.197863.
  75. Gorbalenya AE, Lauber C, Siddell S. Taxonomy of Viruses. Elsevier; 2019. https://doi.org/10.1016/b978-0-12-801238-3.99237-7.
  76. International Committee on Taxonomy of Viruses Executive C. The new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks. Nat Microbiol. 2020;5(5):668-674. https://doi.org/10.1038/s41564-020-0709-x.
  77. Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785-6797. https://doi.org/10.1074/jbc.RA120.013679.
  78. Gorla US, Rao GK, Kulandaivelu US, et al. Lead Finding from Selected Flavonoids with Antiviral (SARS-CoV-2) Potentials against COVID-19: An In-silico Evaluation. Comb Chem High Throughput Screen. 2020. https://doi.org/10.2174/1386207323999200818162706.
  79. Gosert R, Kanjanahaluethai A, Egger D, et al. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J Virol. 2002;76(8):3697-3708. https://doi.org/10.1128/jvi.76.8.3697-3708.2002.
  80. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37-48. https://doi.org/10.1002/rmv.483.
  81. Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015;235(2):185-195. https://doi.org/10.1002/path.4454.
  82. Gu H, Chen Q, Yang G, et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science. 2020;369(6511):1603-1607. https://doi.org/10.1126/science.abc4730.
  83. Gupta MK, Vemula S, Donde R, et al. In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. J Biomol Struct Dyn. 2020:1-11. https://doi.org/10.1080/07391102.2020.1751300.
  84. Habtemariam S, Nabavi SF, Banach M, et al. Should We Try SARS-CoV-2 Helicase Inhibitors for COVID-19 Therapy? Arch Med Res. 2020. https://doi.org/10.1016/j.arcmed.2020.05.024.
  85. Hao W, Wojdyla JA, Zhao R, et al. Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathog. 2017;13(6): e1006474. https://doi.org/10.1371/journal.ppat.1006474.
  86. Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol. 2020;38(4):379-381. https://doi.org/10.1038/d41587-020-00003-1.
  87. Hasan A, Paray BA, Hussain A, et al. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J Biomol Struct Dyn. 2020:1-9. https://doi.org/10.1080/07391102.2020. 1754293.
  88. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8. https://doi.org/10.1016/j.cell. 2020.02.052.
  89. Hossen MS, Barek MA, Jahan N, Safiqul Islam M. A Review on Current Repurposing Drugs for the Treatment of COVID-19: Reality and Challenges. SN Compr Clin Med. 2020:1-13. https://doi.org/10.1007/s42399-020- 00485-9.
  90. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/s0140-6736(20)30183-5.
  91. Hurst KR, Koetzner CA, Masters PS. Characterization of a critical interaction between the coronavirus nucleocapsid protein and nonstructural protein 3 of the viral replicase-transcriptase complex. J Virol. 2013;87(16):9159-9172. https://doi.org/10.1128/JVI.01275-13.
  92. Hung IF-N, Lung K-C, Tso EY-K, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;395(10238):1695-1704. https://doi.org/10.1016/s0140-6736(20)31042-4.
  93. Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect. 2020;53(3):436-443. https://doi.org/10.1016/j.jmii.2020.03.034.
  94. Jia X, Yin C, Lu S, et al. Two Things about COVID-19 Might Need Attention. Preprints.org. 2020. https://doi.org/10.20944/preprints202002.0315.v1.
  95. Jiang RD, Liu MQ, Chen Y, et al. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. Cell. 2020;182(1):50-58 e58. https://doi.org/10.1016/j.cell.2020.05.027.
  96. Jimenez-Alberto A, Ribas-Aparicio RM, Aparicio-Ozores G, Castelan-Vega JA. Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors. Comput Biol Chem. 2020;88:107325. https://doi.org/10.1016/j.compbiolchem.2020.107325.
  97. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4. https://doi.org/10.1186/s40779-020-0233-6.
  98. Jin Z, Du X, Xu Y, et al. Structure of M(pro) from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289-293. https://doi.org/10.1038/s41586-020-2223-y.
  99. Jureka AS, Silvas JA, Basler CF. Propagation, Inactivation, and Safety Testing of SARS-CoV-2. Viruses. 2020;12(6). https://doi.org/10.3390/v12060622.
  100. World Health Organization. ICD-11. International Statistical Classification of Diseases and Related Health Problems. WHO; 2018.
  101. talk.ictvonline.org [Internet]. ICTV Code. The International Code of Virus Classification and Nomenclature. October 2018 [cited 2020 Nov 3]. Available from: https://talk.ictvonline.org/information/w/ictv-information/383/ictv-code.
  102. Kapusta K, Kar S, Collins JT, et al. Protein reliability analysis and virtual screening of natural inhibitors for SARS-CoV-2 main protease (Mpro) through docking, molecular mechanic & dynamic, and ADMET profiling. J Biomol Struct Dyn. 2020:1-18. https://doi.org/10.1080/07391102.2020.1806930.
  103. Izaguirre G. The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases. Viruses. 2019;11(9):837. https://doi.org/10.3390/v11090837.
  104. Khalili JS, Zhu H, Mak NSA, et al. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J Med Virol. 2020;92(7):740-746. https://doi.org/10.1002/jmv.25798.
  105. Khan RJ, Jha RK, Amera GM, et al. Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase. J Biomol Struct Dyn. 2020:1-14. https://doi.org/10.1080/07391102.2020.1753577.
  106. Kleine-Weber H, Elzayat MT, Hoffmann M, Pohlmann S. Functional analysis of potential cleavage sites in the MERS-coronavirus spike protein. Sci Rep. 2018;8(1):16597. https://doi.org/10.1038/s41598-018-34859-w.
  107. Kim E, Jensen Z, van Grootel A, et al. Inorganic Materials Synthesis Planning with Literature-Trained Neural Networks. J Chem Inf Model. 2020;60(3):1194-1201. https://doi.org/10.1021/acs.jcim.9b00995.
  108. Kit O, Kit Y. Features of the interaction of human defensins with the SARS-CoV-2 spike protein: An in silico comparative analysis. 2020. https://doi.org/10.13140/RG.2.2.22222.41281.
  109. Ko JH, Seok H, Cho SY, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617-622. https://doi.org/10.3851/IMP3243.
  110. Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000Res. 2020;9:72. https://doi.org/10.12688/f1000research.22211.2.
  111. Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953-1966. https://doi.org/10.1056/NEJMoa030781.
  112. Kuba K, Imai Y, Ohto-Nakanishi T, Penninger JM. Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol Ther. 2010;128(1):119-128. https://doi.org/10.1016/j.pharmthera.2010.06.003.
  113. Kumar A, Choudhir G, Shukla SK, et al. Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches. J Biomol Struct Dyn. 2020:1-11. https://doi.org/10.1080/07391102.2020.1772112.
  114. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215-220. https://doi.org/10.1038/s41586-020-2180-5.
  115. Lauber C, Gorbalenya AE. Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses. J Virol. 2012;86(7): 3905-3915. https://doi.org/10.1128/JVI.07174-11.
  116. Lee T-W, Cherney MM, Liu J, et al. Crystal Structures Reveal an Induced-fit Binding of a Substrate-like Aza-peptide Epoxide to SARS Coronavirus Main Peptidase. J Mol Biol. 2007;366(3):916-932. https://doi.org/10.1016/j.jmb.2006.11.078.
  117. Lei J, Kusov Y, Hilgenfeld R. Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein. Antiviral Res. 2018;149:58-74. https://doi.org/10.1016/j.antiviral.2017.11.001.
  118. Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016;3(1):237-261. https://doi.org/10.1146/annurev-virology-110615-042301.
  119. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424-432. https://doi.org/10.1002/jmv.25685.
  120. Li Q, Cao Z, Rahman P. Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations. Mol Genet Genomic Med. 2020;8(8): e1344. https://doi.org/10.1002/mgg3.1344.
  121. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-1207. https://doi.org/10.1056/NEJMoa2001316.
  122. Li Y, Zhang J, Wang N, et al. Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening. bioRxiv. 2020. https://doi.org/10.1101/2020.01.28.922922.
  123. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454. https://doi.org/10.1038/nature02145.
  124. Li W, Sui J, Huang IC, et al. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology. 2007;367(2):367-374. https://doi.org/10.1016/j.virol. 2007.04.035.
  125. Li X, Geng M, Peng Y, et al. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2): 102-108. https://doi.org/10.1016/j.jpha.2020.03.001.
  126. Li Z, Wang X, Cao D, et al. Rapid review for the anti-coronavirus effect of remdesivir. Drug Discov Ther. 2020;14(2): 73-76. https://doi.org/10.5582/ddt.2020.01015.
  127. Liu C, Yang Y, Gao Y, et al. Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM. bioRxiv. 2020. https://doi.org/10.1101/2020.03.02.972927.
  128. Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(9):1025-1031. https://doi.org/10.1097/CM9.0000000000000744.
  129. Liu X, Wang XJ. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. J Genet Genomics. 2020;47(2):119-121. https://doi.org/10.1016/j.jgg.2020.02.001.
  130. Lo MK, Jordan R, Arvey A, et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep. 2017;7:43395. https://doi.org/10.1038/srep43395.
  131. Lovato ECW, Barboza LN, Wietzikoski S, et al. Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19). Curr Pharm Des. 2020. https://doi.org/10.2174/1381612826666200707121636.
  132. Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020;14(1):69-71. https://doi.org/10.5582/bst.2020.01020.
  133. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574. https://doi.org/10.1016/s0140-6736(20)30251-8.
  134. Lu Y, Hardes K, Dahms SO, et al. Peptidomimetic furin inhibitor MI-701 in combination with oseltamivir and ribavirin efficiently blocks propagation of highly pathogenic avian influenza viruses and delays high level oseltamivir resistance in MDCK cells. Antiviral Res. 2015;120:89-100. https://doi.org/10.1016/j.antiviral.2015.05.006.
  135. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015;211(1):80-90. https://doi.org/10.1093/infdis/jiu396.
  136. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034. https://doi.org/10.1016/s0140-6736(20)30628-0.
  137. Ming Y, Qiang L. Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications. SN Compr Clin Med. 2020:1-6. https://doi.org/10.1007/s42399-020-00400-2.
  138. Morgenstern B, Michaelis M, Baer PC, et al. Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun. 2005;326(4):905-908. https://doi.org/10.1016/j.bbrc.2004.11.128.
  139. Mubarak A, Alturaiki W, Hemida MG. Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development. J Immunol Res. 2019;2019:6491738. https://doi.org/10.1155/2019/6491738.
  140. Naqvi AAT, Fatima K, Mohammad T, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165878. https://doi.org/10.1016/j.bbadis.2020.165878.
  141. Nguyen DD, Gao K, Chen J, et al. Potentially highly potent drugs for 2019-nCoV. bioRxiv. 2020. https://doi.org/10.1101/2020.02.05.936013.
  142. Order – Nidovirales. In: Virus Taxonomy. Ninth Report of the International Committee on Taxonomy of Viruses. Ed. by A.M.Q. King, M.J. Adams, E.B. Carstens, E.J. Lefkowitz Elsevier; 2012. P. 784-794. https://doi.org/10.1016/b978-0-12-384684-6.00066-5.
  143. Papa G, Mallery DL, Albecka A, et al. Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion. bioRxiv. 2020. https://doi.org/10.1101/2020.08.13.243303.
  144. Park SJ, Yu KM, Kim YI, et al. Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets. mBio. 2020;11(3). https://doi.org/10.1128/mBio. 01114-20.
  145. Pastorino B, Touret F, Gilles M, et al. Evaluation of Chemical Protocols for Inactivating SARS-CoV-2 Infectious Samples. Viruses. 2020;12(6). https://doi.org/10.3390/v12060624.
  146. Peersen OB. A Comprehensive Superposition of Viral Polymerase Structures. Viruses. 2019;11(8). https://doi.org/10.3390/v11080745.
  147. Plank J, Hsieh TS. Helicase-appended topoisomerases: new insight into the mechanism of directional strand transfer. J Biol Chem. 2009;284(45):30737-30741. https://doi.org/10.1074/jbc.R109.051268.
  148. Pokhrel R, Chapagain P, Siltberg-Liberles J. Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2. J Med Microbiol. 2020;69(6):864-873. https://doi.org/10.1099/jmm. 0.001203.
  149. Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58. https://doi.org/10.1038/nrd.2018.168.
  150. Ramos-Molina B, Lick AN, Nasrolahi Shirazi A, et al. Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors. PLoS One. 2015;10(6): e0130417. https://doi.org/10.1371/journal.pone.0130417.
  151. Raney KD, Sharma SD, Moustafa IM, Cameron CE. Hepatitis C virus non-structural protein 3 (HCV NS3): a multifunctional antiviral target. J Biol Chem. 2010;285(30):22725-22731. https://doi.org/10.1074/jbc.R110.125294.
  152. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395(10223): e30-e31. https://doi.org/10.1016/s0140-6736(20)30304-4.
  153. Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007;30(4):297-308. https://doi.org/10.1016/j.ijantimicag.2007.05.015.
  154. Ruan Y, Wei CL, Ling AE, et al. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet. 2003;361(9371):1779-1785. https://doi.org/10.1016/s0140-6736(03)13414-9.
  155. Sarma P, Shekhar N, Prajapat M, et al. In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J Biomol Struct Dyn. 2020:1-9. https://doi.org/10.1080/07391102.2020.1753580.
  156. Serafin MB, Bottega A, Foletto VS, et al. Drug repositioning is an alternative for the treatment of coronavirus COVID-19. Int J Antimicrob Agents. 2020;55(6):105969. https://doi.org/10.1016/j.ijantimicag.2020.105969.
  157. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA. 2020;117(21):11727-11734. https://doi.org/10.1073/pnas.2003138117.
  158. Shamsi A, Mohammad T, Anwar S, et al. Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy. Biosci Rep. 2020;40(6). https://doi.org/10.1042/BSR20201256.
  159. 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;38(1):10-18. https://doi.org/10.12932/AP-200220-0773.
  160. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. https://doi.org/10.1038/s41467-019-13940-6.
  161. Cui S, Hao W. Deducing the Crystal Structure of MERS-CoV Helicase. Methods Mol Biol. 2020;2099:69-85. https://doi.org/10.1007/978-1-0716-0211-9_6.
  162. Shereen MA, Khan S, Kazmi A, et al. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020;24:91-98. https://doi.org/10.1016/j.jare.2020.03.005.
  163. Shiryaev SA, Remacle AG, Ratnikov BI, et al. Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. J Biol Chem. 2007;282(29):20847-20853. https://doi.org/10.1074/jbc.M703847200.
  164. Sidwell RW, Robins RK, Hillyard IW. Ribavirin: An antiviral agent. Pharmacol Ther. 1979;6(1):123-146. https://doi.org/10.1016/0163-7258(79)90058-5.
  165. Siddell SG, Walker PJ, Lefkowitz EJ, et al. Additional changes to taxonomy ratified in a special vote by the International Committee on Taxonomy of Viruses (October 2018). Arch Virol. 2019;164(3):943-946. https://doi.org/10.1007/s00705-018-04136-2.
  166. Singh TU, Parida S, Lingaraju MC, et al. Drug repurposing approach to fight COVID-19. Pharmacol Rep. 2020. https://doi.org/10.1007/s43440-020-00155-6.
  167. Sivabakya TK, Srinivas G. Will the antimalarial drug take over to combat COVID-19? J Public Health (Berl.) 2020: 1-4. https://doi.org/10.1007/s10389-020-01293-0.
  168. Simmons G, Reeves JD, Rennekamp AJ, et al. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci USA. 2004;101(12):4240-4245. https://doi.org/10.1073/pnas.0306446101.
  169. Skariyachan S, Challapilli SB, Packirisamy S, et al. Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections. Front Microbiol. 2019;10:569. https://doi.org/10.3389/fmicb.2019.00569.
  170. Snijder EJ, Bredenbeek PJ, Dobbe JC, et al. Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage. J Mol Biol. 2003;331(5):991-1004. https://doi.org/10.1016/s0022-2836(03)00865-9.
  171. Song W, Gui M, Wang X, Xiang Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. 2018;14(8):e1007236. https://doi.org/10.1371/journal.ppat.1007236.
  172. Stohlman SA, Baric RS, Nelson GN, et al. Specific interaction between coronavirus leader RNA and nucleocapsid protein. J Virol. 1988;62(11):4288-4295. https://doi.org/10.1128/JVI.62.11.4288-4295.1988.
  173. Sturman LS, Holmes KV, Behnke J. Isolation of coronavirus envelope glycoproteins and interaction with the viral nucleocapsid. J Virol. 1980;33(1):449-462. https://doi.org/10.1128/JVI.33.1.449-462.1980.
  174. Sun S-H, Chen Q, Gu H-J, et al. A Mouse Model of SARS-CoV-2 Infection and Pathogenesis. Cell Host Microbe. 2020;28(1):124-133.e124. https://doi.org/10.1016/j.chom.2020.05.020.
  175. Tai W, He L, Zhang X, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol. 2020;17(6): 613-620. https://doi.org/10.1038/s41423-020-0400-4.
  176. Tobaiqy M, Qashqary M, Al-Dahery S, et al. Therapeutic management of patients with COVID-19: a systematic review. Infection Prevention in Practice. 2020;2(3):100061. https://doi.org/10.1016/j.infpip.2020.100061.
  177. Ton AT, Gentile F, Hsing M, et al. Rapid Identification of Potential Inhibitors of SARS-CoV-2 Main Protease by Deep Docking of 1.3 Billion Compounds. Mol Inform. 2020;39(8): e2000028. https://doi.org/10.1002/minf.202000028.
  178. Tsuji M. Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. FEBS Open Bio. 2020;10(6):995-1004. https://doi.org/10.1002/2211-5463.12875.
  179. Uzunova K, Filipova E, Pavlova V, Vekov T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed Pharmacother. 2020;131:110668. https://doi.org/10.1016/j.biopha.2020.110668.
  180. van Boheemen S, de Graaf M, Lauber C, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio. 2012;3(6). https://doi.org/10.1128/mBio.00473-12.
  181. van Regenmortel MHV. Solving the species problem in viral taxonomy: recommendations on non-Latinized binomial species names and on abandoning attempts to assign metagenomic viral sequences to species taxa. Arch Virol. 2019;164(9):2223-2229. https://doi.org/10.1007/s00705-019-04320-y.
  182. Walls AC, Park YJ, Tortorici MA, et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;181(2):281-292. https://doi.org/10.1016/j.cell.2020.02.058.
  183. Wan Y, Shang J, Sun S, al. Molecular mechanism for antibody-dependent enhancement of coronavirus entry. J Virol. 2020;94(5):e02015-19. https://doi.org/10.1128/JVI.02015-19.
  184. Wang P-H, Cheng Y. Increasing host cellular receptor — Angiotensin-Converting Enzyme 2 (ACE2) expression by Coronavirus may facilitate 2019-nCoV infection. bioRxiv. 2020. https://doi.org/10.1101/2020.02.24.963348.
  185. Wang X, Xu W, Hu G, et al. RETRACTED ARTICLE: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol. 2020. https://doi.org/10.1038/s41423-020-0424-9.
  186. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. bioRxiv. 2020. https://doi.org/10.1101/2020.02.11.944462. (E-publication before print).
  187. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-1263. https://doi.org/10.1126/science.abb2507.
  188. Wu A, Peng Y, Huang B, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;27(3):325-328. https://doi.org/10.1016/j.chom.2020.02.001.
  189. Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020;10(5):766-788. https://doi.org/10.1016/j.apsb.2020.02.008.
  190. Xia S, Liu M, Wang C, et al. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 2020;30(4):343-355. https://doi.org/10.1038/s41422-020- 0305-x.
  191. Xu D, Lu W. Defensins: A Double-Edged Sword in Host Immunity. Front Immunol. 2020;11:764. https://doi.org/10.3389/fimmu.2020.00764.
  192. Pan XW, Xu D, Zhang H, et al. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med. 2020;46(6):1114-1116. https://doi.org/10.1007/s00134-020-06026-1.
  193. Xu Z, Peng C, Shi Y, et al. Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation. bioRxiv. 2020. https://doi.org/10.1101/2020.01.27. 921627.
  194. Xue X, Yu H, Yang H, et al. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. J Virol. 2008;82(5):2515-2527. https://doi.org/10.1128/JVI.02114-07.
  195. Yager EJ. Antibody-dependent enhancement and COVID-19: Moving toward acquittal. Clin Immunol. 2020;217:108496. https://doi.org/10.1016/j.clim.2020.108496.
  196. Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444-1448. https://doi.org/10.1126/science.abb2762.
  197. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-481. https://doi.org/10.1016/s2213-2600(20)30079-5.
  198. Yao TT, Qian JD, Zhu WY, et al. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus – A possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6):556-563. https://doi.org/10.1002/jmv.25729.
  199. Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23(2): 130-137. https://doi.org/10.1111/resp.13196.
  200. Yoshimoto FK. The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J. 2020;39(3):198-216. https://doi.org/10.1007/s10930-020-09901-4.
  201. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814-1820. https://doi.org/10.1056/NEJMoa1211721.
  202. Zaher NH, Mostafa MI, Altaher AY. Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors. Acta Pharm. 2020;70(2):145-159. https://doi.org/10.2478/acph-2020-0024.
  203. Zhang H, Penninger JM, Li Y, et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-590. https://doi.org/10.1007/s00134-020-05985-9.
  204. Zhavoronkov A, Aladinskiy V, Zhebrak A, et al. Potential COVID-2019 3C-like protease inhibitors designed using generative deep learning approaches. ChemRxiv. 2020. https://doi.org/10.26434/chemrxiv.11829102.v2.
  205. Zhavoronkov A, Ivanenkov YA, Aliper A, et al. Deep learning enables rapid identification of potent DDR1 kinase inhibitors. Nat Biotechnol. 2019;37(9):1038-1040. https://doi.org/10.1038/s41587-019-0224-x.
  206. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. https://doi.org/ 10.1038/s41586-020-2012-7.
  207. Zhou Y, Hou Y, Shen J, et al. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:14. https://doi.org/10.1038/s41421-020-0153-3.
  208. Ziebuhr J, Baric RS, Baker S, et al. Proposal 2017.013S. A.v1. Reorganization of the family Coronaviridae into two families, Coronaviridae (including the current subfamily Coronavirinae and the new subfamily Letovirinae) and the new family Tobaniviridae (accommodating the current subfamily Torovirinae and three other subfamilies), revision of the genus rank structure and introduction of a new subgenus rank. 2017.
  209. Ziebuhr J, Baker S, Baric RS, et al. Proposal 2019.021S.Ac.v1. Create ten new species and a new genus in the subfamily Orthocoronavirinae of the family Coronaviridae and five new species and a new genus in the subfamily Serpentovirinae of the family Tobaniviridae. 2019.
  210. Zheng J, Perlman S. Immune responses in influenza A virus and human coronavirus infections: an ongoing battle between the virus and host. Curr Opin Virol. 2018;28: 43-52. https://doi.org/10.1016/j.coviro.2017.11.002.
  211. Zhirnov OP, Klenk HD, Wright PF. Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral Res. 2011;92(1):27-36. https://doi.org/10.1016/j.antiviral.2011.07.014.
  212. Zhou G, Zhao Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. Int J Biol Sci. 2020;16(10):1718-1723. https://doi.org/10.7150/ijbs.45123.
  213. Zhu N, Wang W, Liu Z, et al. Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells. Nat Commun. 2020;11(1). https://doi.org/10.1038/s41467-020-17796-z.
  214. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015;386(9997):995-1007. https://doi.org/10.1016/s0140-6736(15)60454-8.

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