Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Drug Discovery by Drug Repurposing: Combating COVID-19 in the 21st Century

Author(s): Nitesh Sanghai*, Kashfia Shafiq and Geoffrey K. Tranmer

Volume 21, Issue 1, 2021

Published on: 23 August, 2020

Page: [3 - 9] Pages: 7

DOI: 10.2174/1389557520999200824103803

Price: $65

Abstract

Due to the rapidly developing nature of the current COVID-19 outbreak and its almost immediate humanitarian and economic toll, coronavirus drug discovery efforts have largely focused on generating potential COVID-19 drug candidates as quickly as possible. Globally, scientists are working day and night to find the best possible solution to treat the deadly virus. During the first few months of 2020, the SARS-CoV-2 outbreak quickly developed into a pandemic, with a mortality rate that was increasing at an exponential rate day by day. As a result, scientists have turned to a drug repurposing approach to rediscover the potential use and benefits of existing approved drugs. Currently, there is no single drug approved by the U.S. Food and Drug Administration (FDA), for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) that causes COVID-19. Based on only in-vitro studies, several active drugs are already in the clinical pipeline, made possible by following the compassionate use of medical protocols. This method of repurposing and the use of existing molecules like Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, etc. has proven to be a landmark in the field of drug rediscovery. In this review article, we will discuss the repurposing of medicines for treating the deadly novel coronavirus (SARS-CoV-2).

Keywords: Drug discovery, Drug repurposing, Pandemic, SARS-CoV-2, COVID-19, WHO.

« Previous
Graphical Abstract

[1]
Guo, Y.R.; Cao, Q.D.; Hong, Z.S.; Tan, Y.Y.; Chen, S.D.; Jin, H.J.; Tan, K.S.; Wang, D.Y.; Yan, Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil. Med. Res., 2020, 7(1), 11.
[http://dx.doi.org/10.1186/s40779-020-00240-0] [PMID: 32169119]
[2]
Cui, J.; Li, F.; Shi, Z.L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol., 2019, 17(3), 181-192.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[3]
Organisation, W.H. Coronavirus (COVID-19) events as they happen https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
[4]
Ashburn, T.T.; Thor, K.B. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[5]
Scannell, J.W.; Blanckley, A.; Boldon, H.; Warrington, B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat. Rev. Drug Discov., 2012, 11(3), 191-200.
[http://dx.doi.org/10.1038/nrd3681] [PMID: 22378269]
[6]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[7]
Waring, M.J.; Arrowsmith, J.; Leach, A.R.; Leeson, P.D.; Mandrell, S.; Owen, R.M.; Pairaudeau, G.; Pennie, W.D.; Pickett, S.D.; Wang, J.; Wallace, O.; Weir, A. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov., 2015, 14(7), 475-486.
[http://dx.doi.org/10.1038/nrd4609] [PMID: 26091267]
[8]
Parvathaneni, V.; Kulkarni, N.S.; Muth, A.; Gupta, V. Drug repurposing: A promising tool to accelerate the drug discovery process. Drug Discov. Today, 2019, 24(10), 2076-2085.
[http://dx.doi.org/10.1016/j.drudis.2019.06.014] [PMID: 31238113]
[9]
Konreddy, A.K.; Rani, G.U.; Lee, K.; Choi, Y. Recent drug-repurposing-driven advances in the discovery of novel antibiotics. Curr. Med. Chem., 2019, 26(28), 5363-5388.
[http://dx.doi.org/10.2174/0929867325666180706101404 ] [PMID: 29984648]
[10]
Breckenridge, A.; Jacob, R. Overcoming the legal and regulatory barriers to drug repurposing. Nat. Rev. Drug Discov., 2019, 18(1), 1-2.
[http://dx.doi.org/10.1038/nrd.2018.92] [PMID: 29880920]
[11]
Oprea, T.I.; Bauman, J.E.; Bologa, C.G.; Buranda, T.; Chigaev, A.; Edwards, B.S.; Jarvik, J.W.; Gresham, H.D.; Haynes, M.K.; Hjelle, B.; Hromas, R.; Hudson, L.; Mackenzie, D.A.; Muller, C.Y.; Reed, J.C.; Simons, P.C.; Smagley, Y.; Strouse, J.; Surviladze, Z.; Thompson, T.; Ursu, O.; Waller, A.; Wandinger-Ness, A.; Winter, S.S.; Wu, Y.; Young, S.M.; Larson, R.S.; Willman, C.; Sklar, L.A. drug repurposing from an academic perspective. Drug Discov. Today Ther. Strateg., 2011, 8(3-4), 61-69.
[http://dx.doi.org/10.1016/j.ddstr.2011.10.002] [PMID: 22368688]
[12]
Rosa, S.G.V.; Santos, W.C. Clinical trials on drug repositioning for COVID-19 treatment. Rev. Panam. Salud Publica, 2020, 44e40
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID: 32256547]
[13]
Brazil, R. Repurposing Viagra: the ‘little blue pill’for all ills? Acute Pain, 2019, 10.
[14]
Singhal, S.; Mehta, J.; Desikan, R.; Ayers, D.; Roberson, P.; Eddlemon, P.; Munshi, N.; Anaissie, E.; Wilson, C.; Dhodapkar, M.; Zeddis, J.; Barlogie, B. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med., 1999, 341(21), 1565-1571.
[http://dx.doi.org/10.1056/NEJM199911183412102 ] [PMID: 10564685]
[15]
Urquhart, L. Market watch: Top drugs and companies by sales in 2017. Nat. Rev. Drug Discov., 2018, 17(4), 232.
[http://dx.doi.org/10.1038/nrd.2018.42] [PMID: 29588516]
[16]
Fouchier, R.A.; Kuiken, T.; Schutten, M.; van Amerongen, G.; van Doornum, G.J.; van den Hoogen, B.G.; Peiris, M.; Lim, W.; Stöhr, K.; Osterhaus, A.D. Aetiology: Koch’s postulates fulfilled for SARS virus. Nature, 2003, 423(6937), 240.
[http://dx.doi.org/10.1038/423240a] [PMID: 12748632]
[17]
Cascella, M.; Rajnik, M.; Cuomo, A.; Dulebohn, S.C.; Di Napoli, R. Features, Evaluation and Treatment Coronavirus (COVID-19) In: StatPearls, StatPearls Publishing; LLC.: Treasure Island (FL), , 2020.
[18]
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.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5 ] [PMID: 31986264]
[19]
Organisation, W.H. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: Interim guidance, https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected
[20]
Zumla, A.; Chan, J.F.; Azhar, E.I.; Hui, D.S.; Yuen, K.Y. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov., 2016, 15(5), 327-347.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[21]
Hodgson, J. The pandemic pipeline. Nat. Biotechnol., 2020, 38(5), 523-532.
[http://dx.doi.org/10.1038/d41587-020-00005-z] [PMID: 32203293]
[22]
Al-Tawfiq, J.A.; Al-Homoud, A.H.; Memish, Z.A. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med. Infect. Dis., 2020, 34101615
[http://dx.doi.org/10.1016/j.tmaid.2020.101615] [PMID: 32145386]
[23]
de Wilde, A.H.; Jochmans, D.; Posthuma, C.C.; Zevenhoven-Dobbe, J.C.; van Nieuwkoop, S.; Bestebroer, T.M.; van den Hoogen, B.G.; Neyts, J.; Snijder, E.J. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother., 2014, 58(8), 4875-4884.
[http://dx.doi.org/10.1128/AAC.03011-14] [PMID: 24841269]
[24]
Dyall, J.; Coleman, C.M.; Hart, B.J.; Venkataraman, T.; Holbrook, M.R.; Kindrachuk, J.; Johnson, R.F.; Olinger, G.G., Jr; Jahrling, P.B.; Laidlaw, M.; Johansen, L.M.; Lear-Rooney, C.M.; Glass, P.J.; Hensley, L.E.; Frieman, M.B. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob. Agents Chemother., 2014, 58(8), 4885-4893.
[http://dx.doi.org/10.1128/AAC.03036-14] [PMID: 24841273]
[25]
Elshabrawy, H.A.; Fan, J.; Haddad, C.S.; Ratia, K.; Broder, C.C.; Caffrey, M.; Prabhakar, B.S. Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. J. Virol., 2014, 88(8), 4353-4365.
[http://dx.doi.org/10.1128/JVI.03050-13] [PMID: 24501399]
[26]
Gns, H.S.; Gr, S.; Murahari, M.; Krishnamurthy, M. An update on Drug Repurposing: Re-written saga of the drug’s fate. Biomed. Pharmacother., 2019, 110, 700-716.
[http://dx.doi.org/10.1016/j.biopha.2018.11.127] [PMID: 30553197]
[27]
Pinto, J.A.; Capparelli, E.V.; Warshaw, M.; Zimmer, B.; Cressey, T.R.; Spector, S.A.; Qin, M.; Smith, B.; Siberry, G.K.; Mirochnick, M. IMPAACT P1083 Team. A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines. Pediatr. Infect. Dis. J., 2018, 37(2), e29-e35.
[http://dx.doi.org/10.1097/INF.0000000000001817 ] [PMID: 29088027]
[28]
Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res., 2020, 178104787
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[29]
Crump, A.; Ōmura, S. Ivermectin, ‘wonder drug’ from Japan: the human use perspective. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2011, 87(2), 13-28.
[http://dx.doi.org/10.2183/pjab.87.13] [PMID: 21321478]
[30]
te Velthuis, A.J.; van den Worm, S.H.; Sims, A.C.; Baric, R.S.; Snijder, E.J.; van Hemert, M.J. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog., 2010, 6(11)e1001176
[http://dx.doi.org/10.1371/journal.ppat.1001176] [PMID: 21079686]
[31]
Macknin, M.L.; Piedmonte, M.; Calendine, C.; Janosky, J.; Wald, E. Zinc gluconate lozenges for treating the common cold in children: A randomized controlled trial. JAMA, 1998, 279(24), 1962-1967.
[http://dx.doi.org/10.1001/jama.279.24.1962] [PMID: 9643859]
[32]
Scholz, M.; Derwand, R. Does Zinc Supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win todays battle against COVID-19? 2020.
[33]
Medscape, Chloroquine Zinc Trials Underway for COVID-19 Prophylaxis, https://www.medscape.com/viewarticle/928472
[34]
National Library of Medicine. A Study of Hydroxychloroquine Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection (HELPCOVID-19), https://clinicaltrials.gov/ct2/show/NCT04335084
[35]
Chang, J.S.; Wang, K.C.; Yeh, C.F.; Shieh, D.E.; Chiang, L.C. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J. Ethnopharmacol., 2013, 145(1), 146-151.
[http://dx.doi.org/10.1016/j.jep.2012.10.043] [PMID: 23123794]
[36]
Obata, K.; Kojima, T.; Masaki, T.; Okabayashi, T.; Yokota, S.; Hirakawa, S.; Nomura, K.; Takasawa, A.; Murata, M.; Tanaka, S.; Fuchimoto, J.; Fujii, N.; Tsutsumi, H.; Himi, T.; Sawada, N. Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells. PLoS One, 2013, 8(9)e70225
[http://dx.doi.org/10.1371/journal.pone.0070225] [PMID: 24058438]
[37]
Heagy, W.; Crumpacker, C.; Lopez, P.A.; Finberg, R.W. Inhibition of immune functions by antiviral drugs. J. Clin. Invest., 1991, 87(6), 1916-1924.
[http://dx.doi.org/10.1172/JCI115217] [PMID: 1904068]
[38]
Okuda, Y. Review of tocilizumab in the treatment of rheumatoid arthritis. Biologics, 2008, 2(1), 75-82.
[http://dx.doi.org/10.2147/BTT.S1828] [PMID: 19707430]
[39]
Schmidt, R.L.; Jutz, S.; Goldhahn, K.; Witzeneder, N.; Gerner, M.C.; Trapin, D.; Greiner, G.; Hoermann, G.; Steiner, G.; Pickl, W.F.; Burgmann, H.; Steinberger, P.; Ratzinger, F.; Schmetterer, K.G. Chloroquine inhibits human CD4+ T-cell activation by AP-1 signaling modulation. Sci. Rep., 2017, 7, 42191.
[http://dx.doi.org/10.1038/srep42191] [PMID: 28169350]
[40]
Pantziarka, P.; Sukhatme, V.; Bouche, G.; Meheus, L.; Sukhatme, V.P. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience, 2016, 10, 610.
[http://dx.doi.org/10.3332/ecancer.2016.610] [PMID: 26823679]
[41]
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N. Engl. J. Med., 2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[42]
Gilead Sciences, I. Gilead Sciences Initiates Two Phase 3 Studies of Investigational Antiviral Remdesivir for the Treatment of COVID-19, https://www.gilead.com/news-and-press/press-room/press-releases/2020/2/gilead-sciences-initiates-two-phase-3-studies-of-investigational-antiviral-remdesivir-for-the-treatment-of-covid-19
[43]
Touret, F.; de Lamballerie, X. Of chloroquine and COVID-19. Antiviral Res., 2020, 177104762
[http://dx.doi.org/10.1016/j.antiviral.2020.104762 ] [PMID: 32147496]
[44]
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. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents, 2020.105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949 ] [PMID: 32205204]
[45]
National Library of Medicine Tocilizumab in COVID-19 Pneumonia (TOCIVID-19) (TOCIVID-19) https://www.clinicaltrials.gov/ct2/show/NCT04317092
[46]
National Library of Medicine BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE). https://clinicaltrials.gov/ct2/show/NCT04327206
[47]
Juurlink, D.N. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ, 2020, 192(17), E450-E453.
[http://dx.doi.org/10.1503/cmaj.200528] [PMID: 32269021]
[48]
National Library of Medicine A Study of Quintuple Therapy to Treat COVID-19 Infection (HAZDpaC). https://clinicaltrials.gov/ct2/show/NCT04334512
[49]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[50]
National Library of Medicine. Efficacy and Safety of Corticosteroids in COVID-19 https://clinicaltrials.gov/ct2/show/NCT04273321?cond=COVID-19&draw=7
[51]
National Library of Medicine Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel (EPICOS). https://clinicaltrials.gov/ct2/show/NCT04334928
[52]
National Library of Medicine Hydroxychloroquine vs Nitazoxanide in Patients With COVID-19. https://clinicaltrials.gov/ct2/show/NCT04341493
[53]
Fan, H. H.; Wang, L. Q.; Liu, W. L.; An, X. P.; Liu, Z. D.; He, X. Q.; Song, L. H.; Tong, Y. G. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin. Med. J. (Engl)., 2020.
[54]
Cai, Q.; Yang, M.; Liu, D.; Chen, J.; Shu, D.; Xia, J.; Liao, X.; Gu, Y.; Cai, Q.; Yang, Y.; Shen, C.; Li, X.; Peng, L.; Huang, D.; Zhang, J.; Zhang, S.; Wang, F.; Liu, J.; Chen, L.; Chen, S.; Wang, Z.; Zhang, Z.; Cao, R.; Zhong, W.; Liu, Y.; Liu, L. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing), 2020.
[http://dx.doi.org/10.1016/j.eng.2020.03.007] [PMID: 32346491]
[55]
National Library of Medicine A Prospective/Retrospective. Randomized Controlled Clinical Study of Antiviral Therapy in the 2019-nCoV Pneumonia 2019.https://clinicaltrials.gov/ct2/show/NCT04255017
[56]
Langlois, P.L.; Manzanares, W.; Adhikari, N.K.J.; Lamontagne, F.; Stoppe, C.; Hill, A.; Heyland, D.K.; Vitamin, C.; Vitamin, C. Administration to the Critically Ill: A Systematic review and meta-analysis. JPEN J. Parenter. Enteral Nutr., 2019, 43(3), 335-346.
[http://dx.doi.org/10.1002/jpen.1471] [PMID: 30452091]
[57]
Hart, B.J.; Dyall, J.; Postnikova, E.; Zhou, H.; Kindrachuk, J.; Johnson, R.F.; Olinger, G.G.; Frieman, M.B.; Holbrook, M.R.; Jahrling, P.B.; Hensley, L. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol., 2014, 95(Pt 3), 571-577.
[http://dx.doi.org/10.1099/vir.0.061911-0] [PMID: 24323636]
[58]
Drug Discovery from Technology Networks Phase 2 Clinical Trial of APN01 for Treatment of COVID-19 Inititated. https://www.technologynetworks.com/drug-discovery/news/phase-2-clinical-trial-of-apn01-for-treatment-of-covid-19-inititated-332897
[59]
[60]
University of Manitoba News Flattening the Curve. UM researchers launch province’s first clinical trial to combat COVID-19., https://news.umanitoba.ca/flattening-the-curve-um-researchers-launch-provinces-first-clinical-trial-to-combat-covid-19/
[61]
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.; McDonald, E.G.; Rajasingham, R.; Lee, T.C.; Hullsiek, K.H. A Randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N. Engl. J. Med., 2020.
[http://dx.doi.org/10.1056/NEJMoa2016638] [PMID: 32492293]
[62]
Mehra, M.R.; Ruschitzka, F.; Patel, A.N. Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet, 2020, 395(10240), 1820.
[http://dx.doi.org/10.1016/S0140-6736(20)31324-6 ] [PMID: 32511943]
[63]
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.; Ding, D.; Wu, F.; Tang, X.; Ye, X.; Ye, Y.; Liu, B.; Yang, J.; Yin, W.; Wang, A.; Fan, G.; Zhou, F.; Liu, Z.; Gu, X.; Xu, J.; Shang, L.; Zhang, Y.; Cao, L.; Guo, T.; Wan, Y.; Qin, H.; Jiang, Y.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Cao, B.; Wang, C. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 2020, 395(10236), 1569-1578.
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9 ] [PMID: 32423584]
[64]
Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; Lopez de Castilla, D.; Finberg, R.W.; Dierberg, K.; Tapson, V.; Hsieh, L.; Patterson, T.F.; Paredes, R.; Sweeney, D.A.; Short, W.R.; Touloumi, G.; Lye, D.C.; Ohmagari, N.; Oh, M-d.; Ruiz-Palacios, G.M.; Benfield, T.; Fätkenheuer, G.; Kortepeter, M.G.; Atmar, R.L.; Creech, C.B.; Lundgren, J.; Babiker, A.G.; Pett, S.; Neaton, J.D.; Burgess, T.H.; Bonnett, T.; Green, M.; Makowski, M.; Osinusi, A.; Nayak, S.; Lane, H.C. Remdesivir for the Treatment of Covid-19 — Preliminary Report. N. Engl. J. Med., 2020.
[http://dx.doi.org/10.1056/NEJMoa2007764]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy