Insights into the Severe Acute Respiratory Syndrome Coronavirus-2: Transmission, Genome Composition, Replication, Diagnostics and Therapeutics

Main Article Content

Rubi Gupta
Ricky Raj Paswan
Richita Saikia
Basanta Kumar Borah

Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2, originated in Wuhan, China in late 2019 has created a massive pandemic; the disease manifested by the virus was named as COVID-19 by World Health Organization. It has appeared as an unprecedented threat against the global health scenario, as well as the world socio-economic-political structure. The infection of the plausibly animate-origin virus, per se, is not dangerous; but its extremely contagious and infectious nature is the major challenge it has posed. In human, the viral receptor is angiotensin converting enzyme-2, which is present in the cellular membranes of multiple vital organs. The virus has different longevity in different contaminated surfaces which are the principal modes of its transmission. No immunity has so far been reported against the virus; however, immuno-compromised individuals are more vulnerable. For its diagnosis, mainly reverse transcription-based diagnosis is presently being used; however, serological diagnosis is still not a regular practice due to several reasons. Multiple public as well as private sector organizations are working towards vaccine development; research for antiviral drugs and drug-repurposing is also in progress. Several candidate vaccines and drugs are now in various levels of clinical trials. Here, we summarize the scientific basis of the pandemic; its diagnosis, treatment and efforts towards therapeutic development. These efforts will prove useful against future emerging and re-emerging human and non-human epidemics as well as pandemics.

Keywords:
SARS-CoV-2, COVID-19, therapy, treatment, coronavirus

Article Details

How to Cite
Gupta, R., Paswan, R. R., Saikia, R., & Borah, B. K. (2020). Insights into the Severe Acute Respiratory Syndrome Coronavirus-2: Transmission, Genome Composition, Replication, Diagnostics and Therapeutics. Current Journal of Applied Science and Technology, 39(21), 71-91. https://doi.org/10.9734/cjast/2020/v39i2130825
Section
Review Article

References

Anderson RM, Fraser C, Ghani AC, Donnelly CA, Riley S, Ferguson NM, Leung GM, Lam TH, et al. Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic. Philosophical Transactions of the Royal Society of London. Series B: Biol. Sci. 2004;359(1447):1091-105.

Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, Baghbanzadeh M, Aghamohammadi N, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: What lessons have we learned? Int J Epidemiol; 2020.

DOI: 10.1093/ije/dyaa033

World Economic Outlook, International Monetary Fund; April 14, 2020.

South Asia Economic Focus.

Available:https://www.worldbank.org/en/region/sar/overview

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, et al. China Novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.

Smith RD. Responding to global infectious disease outbreaks: Lessons from SARS on the role of risk perception, communication and management. Soc Sci Med. 2006; 63(12):3113-23.

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798):265-9.

Ali SA, Baloch M, Ahmed N, Ali AA, Iqbal A. The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat. J Infect Public Health. 2020; 13(4):644-646.

Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, Mazet JK, Hu B, Zhang W, Peng C, Zhang YJ. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535-8.

Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007;20(4):660-94.

Webster RG. Wet markets—a continuing source of severe acute respiratory syndrome and influenza? The Lancet. 2004;363(9404):234-6.

Che XY, Di B, Zhao GP, Wang YD, Qiu LW, Hao W, Wang M, Qin PZ, et al. A patient with asymptomatic Severe Acute Respiratory Syndrome (SARS) and antigenemia from the 2003–2004 community outbreak of SARS in Guangzhou, China. Clin Infect Dis. 2006; 43(1):e1-5.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.

Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19). Stat Pearls: Treasure Island; 2020.

[Epub ahead of print March 20, 2020].

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with a typical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9(1):221-36.

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;27(3):325–8.

de Wit E, Van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14(8):523.

Tyrrell DA, Bynoe ML. Cultivation of viruses from a high proportion of patients with colds. The Lancet. 1966;1(7428):76–7.

Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23(2):130-7.

Yang Y, Peng F, Wang R, Guan K, Jiang T, Xu G, Sun J, Chang C. The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. J Autoimmun. 2020;102434.

Li B, Si HR, Zhu Y, Yang XL, Anderson DE, Shi ZL, et al. Discovery of bat coronaviruses through surveillance and probe capture-based next-generation sequencinG. mSphere. 2020;5(1):1–11.

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (CoVID-19) from publicly reported confirmed cases: Estimation and application. Ann Intern Med. 2020;172(9): 577–82.

Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic transmission of SARS-CoV-2-Singapore. Morb Mortal Wkly Rep. 2020;69(14):411–5.

Chan JFW, Yuan S, Kok KH, To KKW, 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. The Lancet. 2020;395(10223):514–23.

Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner NW, Ke R. The novel coronavirus, 2019-nCoV, is highly contagious and more infectious than initially estimated. arXiv preprint arXiv:2002.03268; 2020.

Available:http://arxiv.org/abs/2002.03268

Liu YC, Kuo RL, Shih SR. COVID-19: The first documented coronavirus pandemic in history. Biomed J. Press. 2020;1–6.

Knoops K, Kikkert M, Van Den Worm SHE, Zevenhoven-Dobbe JC, Van Der Meer Y, Koster AJ, et al. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 2008; 6(9):1957–74.

Romano M, Ruggiero A, Squeglia F, Maga G, Berisio R. A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells. 2020;9(5):1267.

Snijder EJ, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. 1st Ed. Vol. 96, Advances in Virus Research. Elsevier Inc. 2016;59–126.

Perlman S, Netland J. Coronaviruses post-SARS: Update on replication and pathogenesis. Nat Rev Microbiol. 2009; 7(6):439–50.

Fung TS, Liu DX. Human coronavirus: host-pathogen interaction. Annu Rev Microbiol. 2019;73:529-57.

Yu F, Du L, Ojcius DM, Pan C, Jiang S. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect. 2020;22(2):74–9.

Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, et al. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 2013;23(8):986–93.

de Groot RJ, Luytjes W, Horzinek MC, van der Zeijst BA, Spaan WJ, Lenstra JA Evidence for a coiled-coil structure in the spike proteins of coronaviruses. J Mol Biol. 1987;196(4):963-6

Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 Activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol. 2011;85(9):4122–34.

Armstrong J, Niemann H, Smeekens S, Rottier P, Warren G. Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus. Nature. 1984;308(5961):751–2.

Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, et al. A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol. 2011;174(1):11–22.

Fehr AR, Perlman S. Coronaviruses: An Overview of Their Replication and Pathogenesis. In: Maier HJ, Bickerton E, Britton P, editors. Coronaviruses: methods and protocols. New York, NY: Springer New York; 2015;1–23.

Escors D, Ortego J, Enjuanes L. The membrane M protein of the transmissible gastroenteritis coronavirus binds to the internal core through the carboxy-terminus. Adv Exp Med Biol. 2001;494(3):589– 93.

Vennema H, Godeke GJ, Rossen JW, Voorhout WF, Horzinek MC, Opstelten DJ, et al. Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J. 1996;15(8):2020–8.

Venkatagopalan P, Daskalova SM, Lopez LA, Dolezal KA, Hogue BG. Coronavirus envelope (E) protein remains at the site of assembly. Virology. 2015;478:75–85.

DeDiego ML, Álvarez E, Almazán F, Rejas MT, Lamirande E, Roberts A, et al. A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. J Virol. 2007;81(4):1701–13.

McBride R, van Zyl M, Fielding BC. The coronavirus nucleocapsid is a multifunctional protein. Viruses. 2014;6(8): 2991–3018.

Chang CK, Sue SC, Yu TH, Hsieh CM, Tsai CK, Chiang YC, et al. Modular organization of SARS coronavirus nucleocapsid protein. J Biomed Sci. 2006; 13(1):59–72.

Phan T. Genetic diversity and evolution of SARS-CoV-2. Infect Genet Evol. 2020;81: 104260.

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.

Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020;94(7):1–9.

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; 382(13):119

Raj VS, Mou H, Smits SL, Dekkers DHW, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251–4.

Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. BioRxiv; 2020.

Available:https://doi.org/10.1101/2020.03.14.988345

Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, 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):1-0.

Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7.

Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14(2):185–92.

Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci USA. 2009;106(14):5871–6.

Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020; 5(4):562–9.

Sawicki SG, Sawicki DL. Coronavirus transcription: a perspective. Curr Top Microbiol Immunol. 2005;287:31–55.

Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020;24:91–8.

Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, Levantovsky R, Malle L, et al. Immunology of COVID-19: current state of the science. Immunity. 2020;52(6): 910-41.

Cano RL, Lopera HD. Introduction to T and B lymphocytes. In Autoimmunity: From Bench to Bedside. El Rosario University Press; 2013.

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-8.

Sun B, Feng Y, Mo X, Zheng P, Wang Q, Li P, Peng P, Liu X et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect. 2020;9.

Available:https://doi.org/10.1080/22221751.2020.1762515

Huang AT, Garcia-Carreras B, Hitchings MD, Yang B, Katzelnick LC, Rattigan SM, Borgert BA, Moreno CA, et al. A systematic review of antibody mediated immunity to coronaviruses: Antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv; 2020.

Available:https://doi.org/10.1101/2020.04.14.20065771.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.

Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brünink S et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.

To KK, Lu L, Yip CC, Poon RW, Fung AM, Cheng A, Lui DH, Ho DT, et al. Additional molecular testing of saliva specimens improves the detection of respiratory viruses. Emerg Microbes Infect. 2017;6(1): 1-7.

Dai WC, Zhang HW, Yu J, Xu HJ, Chen H, Luo SP, Zhang H, Liang LH et al. CT imaging and differential diagnosis of COVID-19. Can Assoc Radiol J. 2020; 71(2):195-200.

Seven suspected positive cases await final result; 5 negative; May 17, 2020.

Available:www.shillongtimes.com

Müller NL, Ooi GC, Khong PL, Zhou LJ, Tsang KW, Nicolaou S. High-resolution CT findings of severe acute respiratory syndrome at presentation and after admission. Am J Roentgenol. 2004;182(1): 39-44.

Woo PC, Lau SK, Wong BH, Tsoi HW, Fung AM, Kao RY, Chan KH, Peiris JM, et al. Differential sensitivities of severe acute respiratory syndrome (SARS) coronavirus spike polypeptide enzyme-linked immunosorbent assay (ELISA) and SARS coronavirus nucleocapsid protein ELISA for serodiagnosis of SARS coronavirus pneumonia. J Clin Microbiol. 2005;43(7):3054-8.

Gronowski AM. Who or what is SHERLOCK? J Intl Fed Clin Chem Lab Med. 2018;29(3):201-204.

Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4):372.

Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, Miao X, Streithorst JA et al. CRISPR–Cas12-based detection of SARS-CoV-2. Nat Biotechnol. 2020;16:1-5.

Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, Peters CJ, Couch RB. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PloS One. 2012;7(4):e35421.

Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020;14(1):69-71.

Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000Research. 2020;9:72.

Haagmans BL, Osterhaus AD. Corona-viruses and their therapy. Antivir Res. 2006;71(2-3):397-403.

Bergman S, Cennimo D, Miller M, Olsen K. Treatment of Coronavirus Disease 2019 (COVID-19): Investigational drugs and other therapies. Medscape. 2020;2019:1–25.

Available:https://emedicine.medscape.com/article/2500116-overview

Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-23.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen 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.

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu 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):766-88.

Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC et al. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent. Sci.2020;6(3):315-331.

Enjuanes L, Zuñiga S, Castano-Rodriguez C, Gutierrez-Alvarez J, Canton J, Sola I. Molecular basis of coronavirus virulence and vaccine development. Adv Virus Res. Academic Press. 2016;96: 245-286.

Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: an overview. Curr Trop Med Rep. 2020;7:61-4.

Cheung E. China coronavirus: Hong Kong researchers have already developed vaccine but need time to test it, expert reveals. South China Morning Post; 2020.

Available:https://www.scmp.com/news/hong-kong/health-environment/article/3047956/china-coronavirus-hongkong-researchers-have

Accessed 28 Feb, 2020.

Shieber J. Codagenix raises $20 million for a new flu vaccine and other therapies. Tech Crunch; 2020.

Available:https://techcrunch.com/2020/01/13/ codagenix-raises-20-million-for-a-new-flu-vaccine-and-othertherapies

www.natureasia.com. When ready, a coronavirus vaccine must reach all; 2020.

Available:https://www.natureasia.com/en/nindia/article/10.1038/nindia.2020.81.

GlaxoSmithKline press release; 2020.

Available:https://www.gsk.com/en-gb/media/press-releases/clover-and-gsk-announce-research-collaboration-to-evaluate-coronavirus-covid-19-vaccine-candidate-with-pandemic-adjuvant-system

Jiang S, Bottazzi ME, Du L, Lustigman S, Tseng CT, Curti E, Jones K, Zhan B et al. Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome. Expert Rev. Vaccines. 2012;11(12):1405-13.

Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H. The architecture of SARS-CoV-2 transcriptome. Cell. 2020;181(4):1–8.

Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, Collins PL. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. PNAS. 2004;101(26):9804-9.

Cattani M. Global coalition to accelerate COVID-19 clinical research in resource-limited settings. The Lancet. 2020;395: 1322-5.

Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, Murphy BR, Rappuoli R et al. An efficient method to make human monoclonal antibodies from memory B cells: Potent neutralization of SARS coronavirus. Nat Med. 2004;10(8):871-5.

Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, Pham DH, Deif H, et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: A preliminary study. J Am Med Assoc. 2003;290(24):3222-8.

Seesuay W, Jittavisutthikul S, Sae-Lim N, Sookrung N, Sakolvaree Y, Chaicumpa W. Human transbodies that interfere with the functions of Ebola virus VP35 protein in genome replication and transcription and innate immune antagonism. Emerg Microbes Infec. 2018;7(1):1-5.

Gilardin L, Bayry J, Kaveri SV. Intravenous immunoglobulin as clinical immune-modulating therapy. Can Med Assoc J. 2015;187(4):257-64.

Kumar V, Jung YS, Liang PH. Anti-SARS coronavirus agents: A patent review (2008–present). Expert Opin Ther Pat. 2013;23(10):1337-48.

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5): 843-54.

Lundstrom K. Coronavirus pandemic - therapy and vaccines. Biomedicine. 2020; 8(5):109.

Shi Y. Mammalian RNAi for the masses. Trends Genet. 2003;19(1):9-12.

Zheng BJ, Guan Y, Tang Q, Du C, Xie FY, He ML, Chan KW, Wong KL et al. Prophylactic and therapeutic effects of small interfering RNA targeting SARS coronavirus. Antivir Ther. 2004;9(3):365-74.

Chang Z, Hu J. RNAi therapeutics: Can siRNAs conquer SARS? Gene Ther. 2006; 13(11):871.

Lu CY, Huang HY, Yang TH, Chang LY, Lee CY, Huang LM. siRNA silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in Vero E6 cells. Eur J Clin Microbiol. 2008;27(8): 709-15.

Millet JK, Nal B. Investigation of the functional roles of host cell proteins involved in coronavirus infection using highly specific and scalable rna interference (RNAi) approach. In Coronaviruses. Humana Press, New York, NY. 2015;231-240.

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD. Convalescent Plasma Study Group, Nguyen-Van-Tam JS, Beck CR. 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.

Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, Ng MH, Chan P et al. Retrospective comparison of convalescent plasma with continuing high‐dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004;10(7): 676-8.

Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52(4):447-56.

Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, Wei P, Ge J, et al. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity. 2020;52(6):1-7.

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;1–9.

Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, Li Y, Zhu L et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science; 2020.

DOI: 10.1126/science.abc1932

Rees V. FDA grants fast track designation to Moderna’s COVID-19 vaccine; 2020.

Available:https://www.europeanpharmaceuticalreview.com/news/119464/fda-grants-fast-track-designation-to-modernas-covid-19-vaccine

Gao ZC. Efficient management of novel coronavirus pneumonia by efficient prevention and control in scientific manner. Zhonghua Jie He He Hu Xi Za Zhi. 2020; 43:E001-E001.

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med; 2020.

Food and Drug Administration; 2020.

Available:https://www.fda.gov/media/137564/download

Available:https://health.economictimes.indiatimes.com/news/policy/who-warns-against-using-hydroxychloroquine-outside-clinical-trials/75858675

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. J Am Med Assoc. 2020;323(18): 1824-36.

Wang X, Cao R, Zhang H, Liu J, Xu M, Hu H, Li Y, Zhao L et al. The anti-influenza virus drug, arbidol is an efficient inhibitor of SARS-CoV-2 in vitro. Cell Discov. 2020; 6(28):1-5.

Pruijssers AJ, Denison MR. Nucleoside analogues for the treatment of coronavirus infections. Curr Opin Virol. 2019;35:57-62.

Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, Kao RY, Poon LL, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax. 2004;59(3):252-6.

Omrani AS, Saad MM, Baig K, Bahloul A, Abdul-Matin M, Alaidaroos AY, Almakhlafi GA, Albarrak MM, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14(11):1090-5.

Jin Z, Zhao Y, Sun Y, Zhang B, Wang H, Wu Y, Zhu Y, Zhu C, et al. Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur. Nat. Struct. Mol Biol. 2020;27(6):529-32.

The Science Ttimes. 'Favilavir': First approved drug to possibly treat Corona-virus; 2020.

Available:https://www.sciencetimes.com/articles/25053/20200317/favilavir-first-approve-drug-treat-coronavirus.htm

Abbott TR, Dhamdhere G, Liu Y, Lin X, Goudy L, Zeng L, Chemparathy A, Chmura S et al. Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and influenza. Cell. 2020;181(4):865-76.

Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD. Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell. 2018;173(3):665-76.

Yan WX, Chong S, Zhang H, Makarova KS, Koonin EV, Cheng DR, Scott DA. Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL-domain-containing accessory protein. Mol Cell. 2018;70(2):327-39.

Pervushin K, Tan E, Parthasarathy K, Lin X, Jiang FL, Yu D, Vararattanavech A, Soong TW, et al. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Pathog. 2009;5(7): e1000511.

Available:https://www.reuters.com/article/us-health-coronavirus-fujifilm-avigan/fujifilm-to-start-phase-ii-clinical-trial-of-avigan-for-covid-19-patients-in-u-s-idUSKCN21R0KF.

Available:https://www.prnewswire.com/in/news-releases/glenmark-to-commence-new-phase-3-clinical-trial-on-combination-of-two-anti-viral-drugs-favipiravir-and-umifenovir-in-hospitalized-patients-of-moderate-covid-19-in-india-836904730.html

Available:https://www.pharmaceutical-technology.com/news/glenmark-favipiravir-covid-nod/

Indian Express. Ayurveda medicine trial to begin on asymptomatic Covid-19 patients in Chandigarh; May 10, 2020.

Available:www.nature.com/articles/d41586-020-01824-5

Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang L, Sun Q, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020;368(6492): 779-782.

Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Series B. 2017;93(7):449-63.

Johnson DE. Biotherapeutics: challenges and opportunities for predictive toxicology of monoclonal antibodies. Int J Mol Sci. 2018;19(11):3685.

Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A, Govindasamy V, Giridharan B, Ganesan S, Venugopal A, et al. COVID-19: A promising cure for the global panic. Sci Total Environ. 2020;725: 138277.

COVID-19 treatment tracker (updated weekly). Milken Institute. 2020-05-05. Available:https://milkeninstitute.org/covid-19-tracker

Retrieved 2020-05-07. Lay summary.

Cure E, Cure MC. Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis. Diabetes Metab Syndr. 2020;14(4):405.