Epidemiology, Virology, Clinical Features, Diagnosis, and Treatment of SARS-CoV-2 Infection

Abstract

Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged and spread quickly worldwide. The disease is generally mild in adult people but in any with comorbidities may proceed to acute respiratory distress syndrome (ARDS), pneumonia, and multi-organ dysfunction. By performing molecular tests on respiratory secretions can diagnose the virus. Elevated C-reactive protein (CRP) and normal/low white cell counts are common laboratory diagnoses of COVID-19 while the tomographic chest scan is usually irregular for many infected people. Some patients progress to respiratory failure, pneumonia, and finally death by the end of the first week of illness because of the sharp rise in inflammatory cytokines such as IL7, IL2, GCSF, IL10, MIP1A, MCP1, IP10, and TNFα. Various approaches to the COVID-19 are being performed by scientists. Use of chemical medical drugs that are effective for other viral infections. Among them, remdesivir was approved by FDA on 1th May 2020 because of its impact to treat patients. Also, several studies have revealed that many Chinese herbal remedies have a remarkable impact on the healing process when simultaneously were used along with pharmacological drugs. In the meantime, many efforts have been made to produce an effective vaccine, and so far, the Ad5-vectored COVID-19 vaccine has been successful and has entered phase 2 in the human trial. The current review focus on epidemiology, virology, clinical features, diagnosis, and available treatment of coronavirus that might assist researchers and clinicians in establishing action options for timely against this infection.

Keywords

• Severe acute respiratory syndrome
• SARS-CoV-2
• COVID-19
• Coronavirus
• Treatment

References

1. 1. Marra MA, Jones SJM, Astell CR, Holt RA, Brooks-Wilson A, Butterfield YSN, et al. The genome sequence of the SARS-associated coronavirus. Science (80- ). 2003;300(5624):1399–404.
2. 2. Al-Tawfiq JA, Zumla A, Memish ZA. Travel implications of emerging coronaviruses: SARS and MERS-CoV. Travel Med Infect Dis. 2014;12(5):422–8.
3. 3. Chan JF-W, To KK-W, Tse H, Jin D-Y, Yuen K-Y. Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends Microbiol. 2013;21(10):544–55.
4. 4. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19). In: StatPearls [Internet]. StatPearls Publishing; 2020.
5. 5. Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020;
6. 6. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–74.
7. 7. Wu D, Zou S, Bai T, Li J, Zhao X, Yang L, et al. Poultry farms as a source of avian influenza A (H7N9) virus reassortment and human infection. Sci Rep. 2015;5:7630.
8. 8. Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019;11(1):59.

9. 9. Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181–92.
10. 10. Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69(4):635–64.
11. 11. Lai MMC. Coronavirus: organization, replication and expression of genome. Annu Rev Microbiol. 1990;44(1):303.
12. 12. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418–23.
13. 13. Holmes K V. SARS-associated coronavirus. N Engl J Med. 2003;348(20):1948–51.
14. 14. de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L, et al. Commentary: Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol. 2013;87(14):7790–2.
15. 15. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;
16. 16. Devaux CA, Rolain J-M, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020;105938.
17. 17. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–23.
18. 18. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. N Engl J Med. 2020;
19. 19. Wu F, Zhao S, Yu B. A new coronavirus associated with human respiratory disease in China.[published on February 03, 2020]. Nature.
20. 20. Giovanetti M, Benvenuto D, Angeletti S, Ciccozzi M. The first two cases of 2019‐nCoV in Italy: Where they come from? J Med Virol. 2020;
21. 21. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol. 2020;79:104212.
22. 22. Li X, Zai J, Zhao Q, Nie Q, Li Y, Foley BT, et al. Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2. J Med Virol. 2020;92(6):602–11.
23. 23. Lee J, Chowell G, Jung E. A dynamic compartmental model for the Middle East respiratory syndrome outbreak in the Republic of Korea: a retrospective analysis on control interventions and superspreading events. J Theor Biol. 2016;408:118–26.
24. 24. Kang CK, Song K-H, Choe PG, Park WB, Bang JH, Kim ES, et al. Clinical and epidemiologic characteristics of spreaders of Middle East respiratory syndrome coronavirus during the 2015 outbreak in Korea. J Korean Med Sci. 2017;32(5):744–9.
25. 25. Yong E. How the pandemic will end. Atl. 2020;
26. 26. Lu H, Stratton CW, Tang Y. Outbreak of Pneumonia of Unknown Etiology in Wuhan China: the Mystery and the Miracle. J Med Virol.
27. 27. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;
28. 28. Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020;9(1):386–9.
29. 29. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
30. 30. Committee GO of NH. Office of State Administration of Traditional Chinese Medicine. Notice on the issuance of a programme for the diagnosis and treatment of novel coronavirus (2019-nCoV) infected pneumonia (Trial Version 4). 2020. 2020.
31. 31. Bergquist SH, Partin C, Roberts DL, O’Keefe JB, Tong EJ, Zreloff J, et al. Non-hospitalized Adults with COVID-19 Differ Noticeably from Hospitalized Adults in Their Demographic, Clinical, and Social Characteristics. SN Compr Clin Med [Internet]. 2020; Available from: https://doi.org/10.1007/s42399-020-00453-3
32. 32. Kui L, Fang Y-Y, Deng Y, Liu W, Wang M-F, Ma J-P, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;
33. 33. Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology. 2020;200230.
34. 34. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–3.
35. 35. Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D, Jin H-J, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Mil Med Res. 2020;7(1):1–10.
36. 36. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama. 2016;315(8):801–10.
37. 37. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457–60.
38. 38. Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science (80- ). 2005;309(5742):1864–8.
39. 39. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;1–5.
40. 40. Iwata-Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N. TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J Virol. 2019;93(6):e01815-18.
41. 41. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao S-Y. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020;
42. 42. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.
43. 43. Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2).
44. 44. Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020;26(4):453–5.
45. 45. Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol. 2005;79(23):14614–21.
46. 46. de Wilde AH, Snijder EJ, Kikkert M, van Hemert MJ. Host factors in coronavirus replication. In: Roles of Host Gene and Non-coding RNA Expression in Virus Infection. Springer; 2017. p. 1–42.
47. 47. Perrier A, Bonnin A, Desmarets L, Danneels A, Goffard A, Rouillé Y, et al. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. J Biol Chem. 2019;294(39):14406–21.
48. 48. Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci. 2005;102(33):11876–81.
49. 49. Lei J, Kusov Y, Hilgenfeld R. Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein. Antiviral Res. 2018;149:58–74. 50. McCloskey B, Heymann DL. SARS to novel coronavirus–old lessons and new lessons. Epidemiol Infect. 2020;148.
50. 51. Wenzhong L, Hualan L. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Prepr https//doi org/1026434/chemrxiv. 2020;11938173:v4.
51. 52. Bornstein SR, Dalan R, Hopkins D, Mingrone G, Boehm BO. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol. 2020;1–2.
52. 53. Song Y, Peng W, Tang D, Dai Y. Protease Inhibitor Use in COVID-19. SN Compr Clin Med [Internet]. 2020; Available from: https://doi.org/10.1007/s42399-020-00448-0
53. 54. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents. J Hosp Infect. 2020; 55. Kashiouris MG, L’Heureux M, Cable CA, Fisher BJ, Leichtle SW. The emerging role of vitamin C as a treatment for sepsis. Nutrients. 2020;12(2):292.
54. 56. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci. 2020;16(10):1708.
55. 57. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018;9(2):e00221-18.
56. 58. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–71.
57. 59. Food and Drug Administration. Remdesivir EUA Letter of Authorization - FDA [Internet]. Vol. 364 KB. 2020. p. 6. Available from: https://www.fda.gov/media/137564/download
58. 60. Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 2006;6(2):67–9.
59. 61. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. 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;
60. 62. Fox R. Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus. 1996;5(1_suppl):4–10.
61. 63. Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012;42(2):145–53.
62. 64. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020;
63. 65. Gautret P, Lagier J-C, Parola P, Meddeb L, Mailhe M, Doudier B, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;105949.
64. 66. Su B, Wang Y, Zhou R, Jiang T, Zhang H, Li Z, et al. Efficacy and Tolerability of Lopinavir/Ritonavir-and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China. Front Pharmacol. 2019;10.
65. 67. Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018;19(1):81.
66. 68. Liu X, Wang X-J. Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines. bioRxiv. 2020;
67. 69. Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018;153:85–94.
68. 70. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58–60.
69. 71. Crumpacker CS. Ganciclovir. N Engl J Med. 1996;335(10):721–9.
70. 72. Shiraki K. Antiviral drugs against alphaherpesvirus. In: Human Herpesviruses. Springer; 2018. p. 103–22.
71. 73. Blaising J, Polyak SJ, Pécheur E-I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res. 2014;107:84–94.
72. 74. Chu CM, Cheng VCC, Hung IFN, Wong MML, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252–6.
73. 75. Rossignol J-F. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014;110:94–103.
74. 76. Hsieh H-P, Hsu JT-A. Strategies of development of antiviral agents directed against influenza virus replication. Curr Pharm Des. 2007;13(34):3531–42.
75. 77. Nishimura H, Yamaya M. A synthetic serine protease inhibitor, Nafamostat Mesilate, is a drug potentially applicable to the treatment of Ebola virus disease. Tohoku J Exp Med. 2015;237(1):45–50.
76. 78. Uyeki TM. Oseltamivir treatment of influenza in children. Oxford University Press US; 2018.
77. 79. Rosa SGV, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Rev Panam Salud Pública. 2020;44.
78. 80. Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis. 2004;7(4):335–45.
79. 81. Santos JR, Curran A, Navarro-Mercade J, Ampuero MF, Pelaez P, Pérez-Alvarez N, et al. Simplification of antiretroviral treatment from darunavir/ritonavir monotherapy to darunavir/cobicistat monotherapy: effectiveness and safety in routine clinical practice. AIDS Res Hum Retroviruses. 2019;35(6):513–8.
80. 82. Mathias AA, German P, Murray BP, Wei L, Jain A, West S, et al. Pharmacokinetics and pharmacodynamics of GS‐9350: a novel pharmacokinetic enhancer without anti‐HIV activity. Clin Pharmacol Ther. 2010;87(3):322–9.
81. 83. Luo Y, Wang C-Z, Hesse-Fong J, Lin J-G, Yuan C-S. Application of Chinese medicine in acute and critical medical conditions. Am J Chin Med. 2019;47(06):1223–35.
82. 84. Hoffmann M, Kleine-Weber H, Krüger N, Mueller MA, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. BioRxiv. 2020;
83. 85. Newfield C. New Medical Indications for Thalidomide and its Derivatives. Sci J Lander Coll Arts Sci. 2018;12(1):3.
84. 86. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China. Clin Immunol. 2020;108393.
85. 87. Markham A, Keam SJ. Danoprevir: First Global Approval. Drugs. 2018;78(12):1271–6.
86. 88. Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet (London, England). 2020;395(10223):e30.
87. 89. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;
88. 90. Sorbera LA, Graul AI, Dulsat C. Taking aim at a fast-moving target: targets to watch for SARS-CoV-2 and COVID-19. Drugs Future. 2020;45(4).
89. 91. Campbell CM, Kahwash R. Will Complement Inhibition be the New Target in Treating COVID-19 Related Systemic Thrombosis? Circulation. 2020;
90. 92. O’Keefe BR, Giomarelli B, Barnard DL, Shenoy SR, Chan PKS, McMahon JB, et al. Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae. J Virol. 2010;84(5):2511–21.
91. 93. Xu Z, Peng C, Shi Y, Zhu Z, Mu K, Wang X, 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;
92. 94. Zhang J, Ma X, Yu F, Liu J, Zou F, Pan T, et al. Teicoplanin potently blocks the cell entry of 2019-nCoV. bioRxiv. 2020;
93. 95. Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Publishing Group; 2020.
94. 96. Fintelman-Rodrigues N, Sacramento CQ, Lima CR, da Silva FS, Ferreira A, Mattos M, et al. Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production. bioRxiv. 2020;
95. 97. Tran DH, Sugamata R, Hirose T, Suzuki S, Noguchi Y, Sugawara A, et al. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A (H1N1) pdm09 virus infection by interfering with virus internalization process. J Antibiot (Tokyo). 2019;72(10):759–68.
96. 98. Deftereos SG, Siasos G, Giannopoulos G, Vrachatis DA, Angelidis C, Giotaki SG, et al. The GReek study in the Effects of Colchicine in COvid-19 complications prevention (GRECCO-19 study): rationale and study design. Hell J Cardiol. 2020;
97. 99. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;
98. 100. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv. 2020;202003(00026):v1.
99. 101. Miao M, De Clercq E, Li G. Clinical significance of chemokine receptor antagonists. Expert Opin Drug Metab Toxicol. 2020;(just-accepted).
100. 102. Cherin P, Marie I, Michallet M, Pelus E, Dantal J, Crave J-C, et al. Management of adverse events in the treatment of patients with immunoglobulin therapy: a review of evidence. Autoimmun Rev. 2016;15(1):71–81.
101. 103. Srinivasan S, Ghosh M, Maity S, Varadarajan R. Broadly neutralizing antibodies for therapy of viral infections. Antib Technol J. 2016;6:1.
102. 104. 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.
103. 105. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. Jama. 2020;323(16):1582–9.
104. 106. Rajendran K, Narayanasamy K, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID‐19: Systematic review. J Med Virol. 2020;
105. 107. Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;
106. 108. Negishi H, Taniguchi T, Yanai H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb Perspect Biol. 2018;10(11):a028423.
107. 109. Guida G, Riccio AM. Immune induction of airway remodeling. In: Seminars in immunology. Elsevier; 2019. p. 101346.
108. 110. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3(9).
109. 111. Francis MJ. Recent advances in vaccine technologies. Vet Clin North Am Small Anim Pract. 2018;48(2):231.
110. 112. Pang J, Wang MX, Ang IYH, Tan SHX, Lewis RF, Chen JI-P, et al. Potential rapid diagnostics, vaccine and therapeutics for 2019 novel coronavirus (2019-nCoV): a systematic review. J Clin Med. 2020;9(3):623.
111. 113. Folegatti PM, Bittaye M, Flaxman A, Lopez FR, Bellamy D, Kupke A, et al. Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial. Lancet Infect Dis. 2020;
112. 114. Zhu F-C, Guan X-H, Li Y-H, Huang J-Y, Jiang T, Hou L-H, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;
113. 115. Chen G-Y, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage–induced immune responses. Science (80- ). 2009;323(5922):1722–5.
114. 116. Toubai T, Rossi C, Oravecz-Wilson K, Zajac C, Liu C, Braun T, et al. Siglec-G represses DAMP-mediated effects on T cells. JCI insight. 2017;2(14).
115. 117. Lisi L, Lacal PM, Barbaccia ML, Graziani G. Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2. Biochem Pharmacol. 2020;114169.
116. 118. Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–33.
117. 119. Gupta N, Krasnodembskaya A, Kapetanaki M, Mouded M, Tan X, Serikov V, et al. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012;67(6):533–9.
118. 120. Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020;11(2):216.
119. 121. Bruno S, Bussolati B, Grange C, Collino F, di Cantogno LV, Herrera MB, et al. Isolation and characterization of resident mesenchymal stem cells in human glomeruli. Stem Cells Dev. 2009;18(6):867–80.
120. 122. Luo H, Tang Q, Shang Y, Liang S, Yang M, Robinson N, et al. Can Chinese medicine be used for prevention of corona virus disease 2019 (COVID-19)? A review of historical classics, research evidence and current prevention programs. Chin J Integr Med. 2020;1–8.
121. 123. Xu X, Zhang Y, Li X, Li XX. Analysis on prevention plan of corona virus disease-19 (COVID-19) by traditional Chinese medicine in various regions. Chin Tradit Herb Drugs. 2020;51:1–8.
122. 124. Ren J, Zhang A-H, Wang X-J. Traditional Chinese medicine for COVID-19 treatment. Pharmacol Res. 2020;155:104743.
123. 125. Verma S. In search of feasible interventions for the prevention and cure of novel Coronavirus disease 2019. 2020;
124. 126. Liu X, Zhang M, He L, Li Y. Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS). Cochrane Database Syst Rev. 2012;(10).
125. 127. Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. 2020; 128. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020;
126. 129. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM‐IgG combined antibody test for SARS‐CoV‐2 infection diagnosis. J Med Virol. 2020;
127. 130. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama. 2020;
128. 131. Organization WH. Coronavirus disease 2019 (COVID-19): situation report, 72. 2020;
129. 132. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6(1):1–4.
130. 133. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;
131. 134. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering. 2020;
132. 135. 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;
133. 136. Abdulamir AS, Hafidh RR. The Possible Immunological Pathways for the Variable Immunopathogenesis of COVID--19 Infections among Healthy Adults, Elderly and Children. Electron J Gen Med. 2020;17(4).
134. 137. Nicastri E, Petrosillo N, Bartoli TA, Lepore L, Mondi A, Palmieri F, et al. National Institute for the Infectious Diseases “L. Spallanzani”, IRCCS. Recommendations for COVID-19 clinical management. Infect Dis Rep. 2020;12(1).
135. 138. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):1–14.
136. 139. Organization WH. SARS: Clinical Trials on Treatment Using a Combination of Traditional Chinese Medicine and Western Medicine. WHO, Geneva, Switz. 2004;1–191.
137. 140. Zhang D, Wu K, Zhang X, Deng S, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J Integr Med. 2020;18(2):152–8.
138. 141. Kumar D, Chandel V, Raj S, Rathi B. In silico identification of potent FDA approved drugs against Coronavirus COVID-19 main protease: A drug repurposing approach. Chem Biol Lett. 2020;7(3):166–75.
139. 142. Srivastava AK, Kumar A, Tiwari G, Kumar R, Misra N. In Silico Investigations on the Potential Inhibitors for COVID-19 Protease. arXiv Prepr arXiv200310642. 2020;
140. 143. Srivastava AK, Kumar A, Misra N. On the Inhibition of COVID-19 Protease by Indian Herbal Plants: An In Silico Investigation. arXiv Prepr arXiv200403411. 2020;
141. 144. Rao P, Shukla A, Parmar P, Goswami D. Proposing a fungal metabolite-Flaviolin as a potential inhibitor of 3CLpro of novel coronavirus SARS-CoV2 using docking and molecular dynamics. arXiv Prepr arXiv200403806. 2020;
142. 145. Arya R, Das A, Prashar V, Kumar M. Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs. 2020;
143. 146. Orlando SJ, Santiago Y, DeKelver RC, Freyvert Y, Boydston EA, Moehle EA, et al. Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology. Nucleic Acids Res. 2010;38(15):e152–e152.
144. 147. Gupta MK, Vadde R. A computational structural biology study to understand the impact of mutation on structure–function relationship of inward-rectifier potassium ion channel Kir6. 2 in human. J Biomol Struct Dyn. 2020;1–14.
145. 148. Gupta MK, Vadde R, Gouda G, Donde R, Kumar J, Behera L. Computational approach to understand molecular mechanism involved in BPH resistance in Bt-rice plant. J Mol Graph Model. 2019;88:209–20.
146. 149. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009;30(16):2785–91.
147. 150. Gupta MK, Vemula S, Donde R, Gouda G, Behera L, Vadde R. In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. J Biomol Struct Dyn. 2020;(just-accepted):1–17.
148. 151. Rani R, Singh A, Pareek A, Tomar S. In Silico Guided Drug Repurposing to Combat SARS-CoV-2 by Targeting Mpro, the Key Virus Specific Protease. 2020;
149. 152. Choudhary S, Malik YS, Tomar S, Tomar S. Identification of SARS-CoV-2 cell entry inhibitors by drug repurposing using in silico structure-based virtual screening approach. Chemrxiv. 2020;
150. 153. Sargunam P, Sridharan S. In-Silico Drug Designing of Novel Morpholino Based Physcion Drug Candidate and Investigation of Inhibition Effects on Covid-19 RNA Dependent-RNA Polymerase Non Structural Protein 12 (Nsp 12) with ADMET Study. 2020;
151. 154. Sterling T, Irwin JJ. ZINC 15–ligand discovery for everyone. J Chem Inf Model. 2015;55(11):2324–37.
152. 155. Haider Z, Subhani MM, Farooq MA, Ishaq M, Khalid M, Khan RSA, et al. In Silico discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 using pharmacophore and molecular docking based virtual screening from ZINC database. Preprints; 2020.
153. 156. Adem S, Eyupoglu V, Sarfraz I, Rasul A, Ali M. Identification of potent COVID-19 main protease (Mpro) inhibitors from natural polyphenols: An in silico strategy unveils a hope against CORONA. 2020;
154. 157. Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, et al. InterPro: the integrative protein signature database. Nucleic Acids Res. 2009;37(suppl_1):D211–5.
155. 158. Dutta K, Shityakov S, Khalifa I, Mal A, Moulik SP, Panda AK, et al. Effects of secondary carbon supplement on biofilm-mediated biodegradation of naphthalene by mutated naphthalene 1, 2-dioxygenase encoded by Pseudomonas putida strain KD9. J Hazard Mater. 2018;357:187–97.
156. 159. Dutta K, Shityakov S, Morozova O, Khalifa I, Zhang J, Panda A, et al. Beclabuvir can inhibit the RNA-dependent RNA polymerase of newly emerged novel coronavirus (SARS-CoV-2). 2020;
157. 160. Boopathirajan PMK, Vijayakumar K. In-Silico Drug Discovery for Covid19 by Targeting Spike Glycoprotein of SARS COV-2 (Wuhan Corona Virus 2019 Outbreak) Against the Docking Analysis with Structure Predicted Human ‘ACE2-FC Region of IGG1’Fusion Protein As a Protein Based Drug. 2020;
158. 161. Xu C, Ke Z, Liu C, Wang Z, Liu D, Zhang L, et al. Systemic in silico screening in drug discovery for Coronavirus Disease (COVID-19) with an online interactive web server. 2020;
159. 162. Lin C-W, Tsai C-H, Tsai F-J, Chen P-J, Lai C-C, Wan L, et al. Characterization of trans‐and cis‐cleavage activity of the SARS coronavirus 3CLpro protease: basis for the in vitro screening of anti‐SARS drugs. FEBS Lett. 2004;574(1–3):131–7.
160. 163. Balmeh N, Mahmoudi S, Mohammadi N, Karabedianhajiabadi A. Predicted therapeutic targets for COVID-19 disease by inhibiting SARS-CoV-2 and its related receptors. Informatics Med Unlocked. 2020;100407.
161. 164. Serseg T, Benarous K, Yousfi M. Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study. arXiv Prepr arXiv200408920. 2020;
162. 165. Fischer A, Sellner M, Neranjan S, Lill MA, Smieško M. Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds. ChemRxiv; 2020.
163. 166. Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev. 2016;101:89–98.
164. 167. Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res. 2014;42(W1):W53–8.
165. 168. Abbasi AM, Ayaz Z, Zainab B. In silico elucidation revealed SARS CoV and MERS CoV Drug Compounds could be Potential Therapeutic Candidates against Post Fusion Core (S2) Protein of Novel Coronavirus (2019-nCov). 2020;