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Abstract

An emerging coronavirus, SARS-CoV-2, is the causative agent for the ongoing pandemic of coronavirus disease 2019 (COVID-19), which has caused a worldwide social and economic disruption. Currently, no antiviral drugs with proven clinical efficacy, or vaccines for its prevention. Therefore, to combat the pandemic of this novel coronavirus, new effective treatments are urgently needed. In the process of traditional drug development, developing new drugs from scratch is a time- consuming process, requires high-investment, and is a high-risk process, which is impractical to face the immediate global challenge of the SARS-CoV-2 pandemic. Drug repurposing strategy is one of the effective ways to quickly find a therapeutic agent for COVID-19 Existing medicines, which already have been tested and proven safe in humans might work for COVID-19 offering a potentially faster approach for the disease management. Here, we review h the latest research progress in epidemiology, viral genome, and life cycles of SARS-CoV-2. Further, we describe and discuss some promising drugs repurposed to target SARS-CoV-2 that are being evaluated in clinical trials.

References

Agrawal, P. (2015). Advantages and Challenges in Drug Re-Profiling. Journal of Pharmacovigilance, S2: e002. 10.4172/2329-6887.S2-e002.

Astuti, I., & Ysrafil. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes & Metabolic Syndrome, 14(4), 407-412.

Boulware, D. R., Pullen, M. F., Bangdiwala, A. S., Pastick, K. A., Lofgren, S. M., Okafor, E. C., Skipper, C. P., Nascene, A. A., Nicol, M. R., Abassi, M., Engen, N. W., Cheng, M. P., LaBar, D., Lother, S. A., MacKenzie, L. J., Drobot, G., Marten, N., Zarychanski, R., Kelly, L. E., Schwartz, I. S., ... Hullsiek, K. H. (2020). A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. The New England Journal of Medicine, NEJMoa2016638.

Cameron, D. W., Japour, A. J., Xu, Y., Hsu, A., Mellors, J., Farthing, C., Cohen, C., Poretz, D., Markowitz, M., Follansbee, S., Angel, J. B., McMahon, D., Ho, D., Devanarayan, V., Rode, R., Salgo, M., Kempf, D. J., Granneman, R., Leonard, J. M., & Sun, E. (1999). Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS (London, England), 13(2), 213–224.

Cantini, F., Niccoli, L., Matarrese, D., Nicastri, E., Stobbione, P., & Goletti, D. (2020). Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. The Journal of Infection, 81(2), 318–356.

Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S. C., & Di Napoli, R. (2020). Features, Evaluation and Treatment Coronavirus (COVID-19). In StatPearls. StatPearls Publishing.

Chan, J. F., Kok, K. H., Zhu, Z., Chu, H., To, K. K., Yuan, S., & Yuen, K. Y. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes & Infections, 9(1), 221–236.

Chan, J. F., To, K. K., Tse, H., Jin, D. Y., & Yuen, K. Y. (2013). Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends in Microbiology, 21(10), 544–555.

de Wit, E., Feldmann, F., Cronin, J., Jordan, R., Okumura, A., Thomas, T., Scott, D., Cihlar, T., & Feldmann, H. (2020). Prophylactic and therapeutic remdesivir (GS- 5734) treatment in the rhesus macaque model of MERS- CoV infection. Proceedings of the National Academy of Sciences of the United States of America, 117(12), 6771–6776.

de Wit, E., van Doremalen, N., Falzarano, D., & Munster, V. J. (2016). SARS and MERS: recent insights into emerging coronaviruses. Nature Reviews Microbiology, 14(8), 523–534.

Fauci, A.S., Lane, H.C., & Redfield, R.R. (2020). Covid- 19-navigating the uncharted. The New England Journal of Medicine, 382(13), 1268–1269.

Gao, J., Tian, Z., & Yang, X. (2020). Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Bioscience Trends, 14(1), 72–73.

Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Sevestre, J., Mailhe, M., Doudier, B., Aubry, C., Amrane, S., Seng, P., Hocquart, M., Eldin, C., Finance, J., Vieira, V. E., Tissot-Dupont, H. T., Honoré, S., Stein, A., Million, M., Colson, P., ... & Raoult, D. (2020). Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Medicine and Infectious Disease, 34, 101663.

Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V. E., Tissot Dupont, H., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J. M., Brouqui, P., & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, 56(1), 105949.

Geleris, J., Sun, Y., Platt, J., Zucker, J., Baldwin, M., Hripcsak, G., Labella, A., Manson, D. K., Kubin, C., Barr, R. G., Sobieszczyk, M. E., & Schluger, N. W. (2020). Observational study of hydroxychloroquine in hospitalized patients with Covid-19. The New England Journal of Medicine, 382(25), 2411–2418.

Gordon, C. J., Tchesnokov, E. P., Feng, J. Y., Porter, D. P., & Götte, M. (2020). The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. The Journal of Biological Chemistry, 295(15), 4773–4779.

Hijikata, A., Shionyu-Mitsuyama, C., Nakae, S., Shionyu, M., Ota, M., Kanaya, S., & Shirai, T. (2020). Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs. FEBS Letters, 594(12), 1960–1973.

Ho, T. Y., Wu, S. L., Chen, J. C., Li, C. C., & Hsiang, C. Y. (2007). Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Research, 74(2), 92–101.

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England), 395(10223), 497–506.

Johns Hopkins Coronavirus Resource Center (CRC). (2020). COVID-19 Map. Retrieved from Johns Hopkins University & Medicine website: https://coronavirus.jhu. edu/map.html.

Kim, A., Sparks, J. A., Liew, J. W., Putman, M. S., Berenbaum, F., Duarte-García, A., Graef, E. R., Korsten, P., Sattui, S. E., Sirotich, E., Ugarte-Gil, M. F., Webb, K., & Grainger, R. (2020). A rush to judgment? rapid reporting and dissemination of results and its consequences regarding the use of hydroxychloroquine for COVID-19. Annals of Internal Medicine, 172(12), 819–821.

Liu, F., Xu, A., Zhang, Y., Xuan, W., Yan, T., Pan, K., Yu, W., & Zhang, J. (2020). Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. International Journal of Infectious Diseases, 95, 183–191.

Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., Li, Y., Hu, Z., Zhong, W., & Wang, M. (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell discovery, 6, 16.

Lo, M. K., Jordan, R., Arvey, A., Sudhamsu, J., Shrivastava-Ranjan, P., Hotard, A. L., Flint, M., McMullan, L. K., Siegel, D., Clarke, M. O., Mackman, R. L., Hui, H. C., Perron, M., Ray, A. S., Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., Chen, J., ... Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England), 395(10224), 565–574.

Lv, Z., Chu, Y., & Wang, Y. (2015). HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV/AIDS (Auckland, N.Z.), 7, 95–104.

Mahévas, M., Tran, V. T., Roumier, M., Chabrol, A., Paule, R., Guillaud, C., Fois, E., Lepeule, R., Szwebel, T. A., Lescure, F. X., Schlemmer, F., Matignon, M., Khellaf, M., Crickx, E., Terrier, B., Morbieu, C., Legendre, P., Dang, J., Schoindre, Y., Pawlotsky, J. M., ... Costedoat- Chalumeau, N. (2020). No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial. MedRxiv, PPR:PPR150909.

Mangum,E.M.,& Graham,K.K.(2001).Lopinavir-Ritonavir: a new protease inhibitor. Pharmacotherapy, 21(11), 1352– 1363.

Mason R. J. (2020). Pathogenesis of COVID-19 from a cell biology perspective. The European Respiratory Journal, 55(4), 2000607.

Millet, J. K., & Whittaker, G. R. (2015). Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Research, 202, 120–134.

Molina, J. M., Delaugerre, C., Le Goff, J., Mela-Lima, B., Ponscarme, D., Goldwirt, L., & de Castro, N. (2020). No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Medecine et Maladies Infectieuses, 50(4), 384.

National Institutes of Health. (2020). NIH clinical trial testing antiviral remdesivir plus anti-inflammatory drug baricitinib for COVID-19 begins. Retrieved from National Institutes of Health website: https://www. nih.gov/news-events/news-releases/nih-clinical-trial- testing-antiviral-remdesivir-plus-anti-inflammatory- drug-baricitinib-covid-19-begins.

Nutho, B., Mahalapbutr, P., Hengphasatporn, K., Pattaranggoon, N. C., Simanon, N., Shigeta, Y., Hannongbua, S., & Rungrotmongkol, T. (2020). Why are lopinavir and ritonavir effective against the newly emerged coronavirus 2019? atomistic insights into the inhibitory Mechanisms. Biochemistry, 59(18), 1769– 1779.

Peiris, J. S., Lai, S. T., Poon, L. L., Guan, Y., Yam, L. Y., Lim, W., Nicholls, J., Yee, W. K., Yan, W. W., Cheung, M. T., Cheng, V. C., Chan, K. H., Tsang, D. N., Yung, R. W., Ng, T. K., Yuen, K. Y., & SARS study group (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet (London, England), 361(9366), 1319–1325.

Porcheddu, R., Serra, C., Kelvin, D., Kelvin, N., & Rubino, S. (2020). Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. Journal of Infection in Developing Countries, 14(2), 125–128.

Qian, Z., Travanty, E. A., Oko, L., Edeen, K., Berglund, A., Wang, J., Ito, Y., Holmes, K. V., & Mason, R. J. (2013). Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome- coronavirus. American Journal of Respiratory Cell and Molecular Biology, 48(6), 742–748.

Rabaan, A. A., Al-Ahmed, S. H., Haque, S., Sah, R., Tiwari, R., Malik, Y. S., Dhama, K., Yatoo, M. I., Bonilla-Aldana, D. K., & Rodriguez-Morales, A. J. (2020). SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Le Infezioni in Medicina, 28(2), 174–184.

Read, J.M., Bridgen, J.R., Cummings, D.A., Ho, A., & Jewell, C.P. (2020). Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions. MedRxiv, PPR:PPR110039.

Roser, M., Ritchie, H., Ortiz-Ospina, E., & Hassel J. (2020). Coronavirus Pandemic (COVID-19). Retrieved from Our World In Data website: https://ourworldindata. org/coronavirus.

Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 109, 102433

Russell, C. D., Millar, J. E., & Baillie, J. K. (2020). Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet (London, England), 395(10223), 473–475.

Sheahan, T. P., Sims, A. C., Graham, R. L., Menachery, V. D., Gralinski, L. E., Case, J. B., Leist, S. R., Pyrc, K., Feng, J. Y., Trantcheva, I., Bannister, R., Park, Y., Babusis, D., Clarke, M. O., Mackman, R. L., Spahn, J. E., Palmiotti, C. A., Siegel, D., Ray, A. S., Cihlar, T., ... Baric, R. S. (2017). Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Science Translational Medicine, 9(396), eaal3653.

Sheahan, T. P., Sims, A. C., Leist, S. R., Schäfer, A., Won, J., Brown, A. J., Montgomery, S. A., Hogg, A., Babusis, D., Clarke, M. O., Spahn, J. E., Bauer, L., Sellers, S., Porter, D., Feng, J. Y., Cihlar, T., Jordan, R., Denison, M. R., & Baric, R. S. (2020). Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS- CoV. Nature Communications, 11(1), 222.

Shereen, M., A., Khan, S., Kazmi, A., Bashir, N., & Siddique, R. (2020). COVID-19 infection: origin, transmission and characteristics of human coronaviruses. Journal of Advanced Research, 24, 91- 98.

Taccone, F. S., Gorham, J., & Vincent, J. L. (2020). Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base. The Lancet. Respiratory Medicine, 8(6), 539–541.

Tao, Y., Tang, L. V., & Hu, Y. (2020). Treatments in the COVID-19 pandemic: an update on clinical trials. Expert Opinion on Emerging Drugs, 25(2), 81–88.

Tortorici, M. A., & Veesler, D. (2019). Structural insights into coronavirus entry. Advances in Virus Research, 105, 93–116.

Touret, F., & de Lamballerie, X. (2020). Of chloroquine and COVID-19. Antiviral Research, 177, 104762.

Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 181(2), 281–292.e6.

Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hu, Z., Zhong, W., & Xiao, G. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research, 30(3), 269–271.

Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., Fu, S., Gao, L., Cheng, Z., Lu, Q., Hu, Y., Luo, G., Wang, K., Lu, Y., Li, H., Wang, S., Ruan, S., Yang, C., Mei, C., Wang, Y., ... Wang, C. (2020). Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet (London, England), 395(10236), 1569–1578.

Wang, Z., Chen, X., Lu, Y., Chen, F., & Zhang, W. (2020). Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Bioscience trends, 14(1), 64–68.

Warren, T. K., Jordan, R., Lo, M. K., Ray, A. S., Mackman, R. L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H. C., Larson, N., Strickley, R., Wells, J., Stuthman, K. S., Van Tongeren, S. A., Garza, N. L., Donnelly, G., Shurtleff, A. C., Retterer, C. J., Gharaibeh, D., ... & Bavari, S. (2016). Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 531(7594), 381–385.

Williamson, B. N., Feldmann, F., Schwarz, B., Meade- White, K., Porter, D. P., Schulz, J., van Doremalen, N., Leighton,I.,KweYinda,C.,Pérez-Pérez,L.,Okumura, A., Lovaglio, J., Hanley, P. W., Saturday, G., Bosio, C. M., Anzick, S., Barbian, K., Cihlar, T., Martens, C., Scott, D. P., ... de Wit, E. (2020). Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv: the preprint server for biology, 2020.04.15.043166.

World Health Organization. (2020). “Solidarity” clinical trial for COVID-19 treatments. Retrieved from World Health Organization website: https://www.who.int/ emergencies/diseases/novel-coronavirus-2019/global- research-on-novel-coronavirus-2019-ncov/solidarity- clinical-trial-for-covid-19-treatments.

World Health Organization. (2020). Pneumonia of unknown cause – China. Retrieved from World Health Organization website: https://www.who.int/csr/don/05- january-2020-pneumonia-of-unkown-cause-china/en/ Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.Y.), 367(6483), 1260–1263.

Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q., Xu, Y., Li, M., Li, X., Zheng, M., Chen, L., & Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica. B, 10(5), 766–788.

Wu, Z., & McGoogan, J. M. (2020). 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, 10.1001/jama.2020.2648

Xu, X., Han, M., Li, T., Sun, W., Wang, D., Fu, B., Zhou, Y., Zheng, X., Yang, Y., Li, X., Zhang, X., Pan, A., & Wei, H. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences of the United States of America, 117(20), 10970–10975.

Yao, T. T., Qian, J. D., Zhu, W. Y., Wang, Y., & Wang, G. Q. (2020). A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. Journal of Medical Virology, 92(6), 556–563.

Ye, Z. W., Yuan, S., Yuen, K. S., Fung, S. Y., Chan, C. P., & Jin, D. Y. (2020). Zoonotic origins of human coronaviruses. International Journal of Biological Sciences, 16(10), 1686–1697.

Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D., & Fouchier, R. A. (2012). Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. The New England Journal of Medicine, 367(19), 1814–1820.

Zhang, W., Zhao, Y., Zhang, F., Wang, Q., Li, T., Liu, Z., Wang, J., Qin, Y., Zhang, X., Yan, X., Zeng, X., & Zhang, S. (2020). The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology (Orlando, Fla.), 214, 108393.

Zhang, Y. Z., & Holmes, E. C. (2020). A Genomic Perspective on the Origin and Emergence of SARS- CoV-2. Cell, 181(2), 223–227.

Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei, Y., Li, H., Wu, X., Xu, J., Tu, S., Zhang, Y., Chen, H., & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England), 395(10229), 1054–1062.

Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., Si, H. R., Zhu, Y., Li, B., Huang, C. L., Chen, H. D., Chen, J., Luo, Y., Guo, H., Jiang, R. D., Liu, M. Q., Chen, Y., Shen, X. R., Wang, X., Zheng, X. S., ... & Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273.

Zumla, A., Chan, J. F., Azhar, E. I., Hui, D. S., & Yuen, K. Y. (2016). Coronaviruses - drug discovery and therapeutic options. Nature reviews. Drug Discovery, 15(5), 327– 347.





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