SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and other Drugs for the Treatment of the New Coronavirus

Author(s): Michele Costanzo, Maria Anna Rachele De Giglio, Giovanni Nicola Roviello*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 27 , 2020


DOI : 10.2174/0929867327666200416131117

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Abstract:

Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.

Keywords: SARS-CoV-2, Coronavirus, COVID-19, antiviral drugs, hydroxychloroquine, remdesivir, favipiravir, lopinavir, ritonavir.

[1]
Wu, J.T.; Leung, K.; Leung, G.M. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet, 2020, The Lancet. 395(10225), 689-697.
[http://dx.doi.org/10.1016/S0140-6736(20)30260-9] [PMID: 32014114]
[2]
Dong, E.; Du, H.; Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis., 2020, 20(5), 533-534.
[http://dx.doi.org/10.1016/s1473-3099(20)30120-1] [PMID: 32087114]
[3]
HUB. Real-time map from Johns Hopkins University, Baltimore(US), 2020.Available at:, https://gisanddata.maps. arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40-299423467 (Accessed: 26 March, 2020)
[4]
World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020 2020.Available at:, https://www.who.int/dg/speeches/ detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020
[5]
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.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[6]
Zhang, L.; Yang, J.R.; Zhang, Z.; Lin, Z. Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission medRxiv, 2020.
[http://dx.doi.org/10.1101/2020.02.25.20027953]
[7]
Cui, Y.; Zhang, Z.F.; Froines, J.; Zhao, J.; Wang, H.; Yu, S.Z.; Detels, R. Air pollution and case fatality of SARS in the People’s Republic of China: an ecologic study. Environ. Health, 2003, 2(1), 15.
[http://dx.doi.org/10.1186/1476-069X-2-15] [PMID: 14629774]
[8]
Lu, H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci. Trends, 2020, 14(1), 69-71.
[http://dx.doi.org/10.5582/bst.2020.01020] [PMID: 31996494]
[9]
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]
[10]
Dayer, M.R.; Taleb-Gassabi, S.; Dayer, M.S. Lopinavir: a potent drug against coronavirus infection: insight from molecular docking study. Arch. Clin. Infect. Dis., 2017, 12(4)e13823
[http://dx.doi.org/10.5812/archcid.13823]
[11]
Wang, Q.; Zhao, Y.; Chen, X.; Hong, A. Virtual screening of approved clinic drugs with main protease (3CLpro) reveals potential inhibitory effects on SARS-CoV-2; Preprints, 2020. 2020030144
[12]
Chen, Y.W.; Yiu, C.B.; Wong, K.Y. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000 Res., 2019, 9, 129.https://dx.doi.org/10.12688%2Ff1000research.22457.2
[PMID: 32194944]
[13]
Ji, S.; Bai, Q.; Wu, X.; Zhang, D.W.; Wang, S.; Shen, J.L.; Fei, G.H. Unique synergistic antiviral effects of Shufeng Jiedu capsule and oseltamivir in influenza A viral-induced acute exacerbation of chronic obstructive pulmonary disease. Biomed. Pharmacother., 2020, 121, 109652.
[http://dx.doi.org/10.1016/j.biopha.2019.109652] [PMID: 31734578]
[14]
New Straits Times. Thailand sees apparent success treating coronavirus with HIV drug 2020.Available at:, https://www.nst.com.my/world/world/2020/02/562079/thailand-sees-apparent-success-treating-coronavirus-hiv-drug
[15]
Sciencemag. WHO launches global megatrial of the four most promising coronavirus treatments 2020.Available at:, https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments
[16]
News. Coronavirus experts explain the symptoms, how it spreads and how to prevent the disease , 2020.Available at:. https://www.abc.net.au/news/2020-01-28/coronavirussymptoms- how-it-spreads-and-how-to-prevent-it/11904062
[17]
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]
[18]
Hoenen, T.; Groseth, A.; Feldmann, H. Therapeutic strategies to target the Ebola virus life cycle. Nat. Rev. Microbiol., 2019, 17(10), 593-606.
[http://dx.doi.org/10.1038/s41579-019-0233-2] [PMID: 31341272]
[19]
Salman, S.; Baiwog, F.; Page-Sharp, M.; Kose, K.; Karunajeewa, H.A.; Mueller, I.; Rogerson, S.J.; Siba, P.M.; Ilett, K.F.; Davis, T.M.E. Optimal antimalarial dose regimens for chloroquine in pregnancy based on population pharmacokinetic modelling. Int. J. Antimicrob. Agents, 2017, 50(4), 542-551.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.05.011] [PMID: 28669839]
[20]
Devaux, C.A.; 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, 55(5), 105938.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[21]
Yao, X.; Ye, F. ; Zhang, M. ; Cui, C.; Huang, B.; Niu, P. ; Liu, X.; Zhao, L.; Dong, E.; Song, C.; Zhan, S.; Lu, R.; Li, H.; Tan, W.; Liu, D. 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., ciaa237.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[22]
Liu, J.; Cao, R.; Xu, M.; Wang, X.; Zhang, H.; Hu, H.; Li, Y.; Hu, Z.; Zhong, W.; Wang, M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov., 2020, 6, 16.
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 32194981]
[23]
The Mainichi. Development of coronavirus treatment advancing in Japan with existing meds, 2020.Available at: , https://mainichi.jp/english/articles/20200317/p2a/00m/0na/026000c
[24]
Gautret, P.; Lagier, J.C.; Parola, P.; Hoang, V.T.; Meddeb, L.; Mailhe, M.; Doudier, B.; Courjon, J.; Giordanengo, V.; Vieira, V.E.; Dupont, H.T.; 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]
[25]
Chinese Clinical Trial Register (ChiCTR). Hydroxychloroquine treating novel coronavirus pneumonia (COVID-19): a multicenter, randomized controlled trial, 2015.Available at:. http://www.chictr.org.cn/showprojen.aspx?proj=49524
[26]
Interim Clinical Guidance For Patients Suspected Of/Confirmed With Covid-19 In Belgium, 2020.Available at:. https://epidemio.wiv isp.be/ID/Documents/Covid19/ COVID-19_InterimGuidelines_Treatment_ENG.pdf? fbclid=IwAR2PP0GEhBHm2m3zH7c- OYFW5kksK3CG6TC40y8em3Z1QVjQ-WNxEWUTyqE
[27]
AIFA (Agenzia Italiana del Farmaco). Azioni intraprese per favorire la ricerca e l’accesso ai nuovi farmaci per il trattamento del COVID-19, 2020. Available at:. https://www.aifa.gov.it/-/azioni-intraprese-per-favorire-laricerca- e-l-accesso-ai-nuovi-farmaci-per-il-trattamento-delcovid- 19
[28]
Ko, W.C.; Rolain, J.M.; Lee, N.Y.; Chen, P.L.; Huang, C.T.; Lee, P.I.; Hsueh, P.R. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int. J. Antimicrob. Agents, 2020, 55(4), 105933.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105933] [PMID: 32147516]
[29]
Holshue, M.L.; DeBolt, C.; Lindquist, S.; Lofy, K.H.; Wiesman, J.; Bruce, H.; Spitters, C.; Ericson, K.; Wilkerson, S.; Tural, A.; Diaz, G.; Cohn, A.; Fox, L.; Patel, A.; Gerber, S.I.; Kim, L.; Tong, S.; Lu, X.; Lindstrom, S.; Pallansch, M.A.; Weldon, W.C.; Biggs, H.M.; Uyeki, T.M.; Pillai, S.K. First Case of 2019 novel coronavirus in the United States. N. Engl. J. Med., 2020, 382(10), 929-936.
[http://dx.doi.org/10.1056/NEJMoa2001191] [PMID: 32004427]
[30]
Gilead Company News And Press; Gilead Sciences Statement on the Company’s Ongoing Response to the 2019 Novel Coronavirus (2019-nCoV/SARS-CoV-2), 2019.Available at:. https://www.gilead.com/news-and-press/companystatements/gilead-sciences-statement-on-the-companyongoing-response-to-the-2019-new-coronavirus
[31]
Ramos-Martín, V.; Johnson, A.; McEntee, L.; Farrington, N.; Padmore, K.; Cojutti, P.; Pea, F.; Neely, M.N.; Hope, W.W. Pharmacodynamics of teicoplanin against MRSA. J. Antimicrob. Chemother., 2017, 72(12), 3382-3389.
[http://dx.doi.org/10.1093/jac/dkx289] [PMID: 28962026]
[32]
Baron, S.A.; Devaux, C.; Colson, P.; Raoult, D.; Rolain, J.M. Teicoplanin: an alternative drug for the treatment of COVID-19? Int. J. Antimicrob. Agents, 2020, 55(4)105944
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105944] [PMID: 32179150]
[33]
Dong, L.; Hu, S.; Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58-60.
[http://dx.doi.org/10.5582/ddt.2020.01012] [PMID: 32147628]
[34]
Nagata, T.; Lefor, A.K.; Hasegawa, M.; Ishii, M. Favipiravir: a new medication for the Ebola virus disease pandemic. Disaster Med. Public Health Prep., 2015, 9(1), 79-81.
[http://dx.doi.org/10.1017/dmp.2014.151] [PMID: 25544306]
[35]
Trieste All News; Coronavirus, will “Tocilizumab” be the drug of hope?, 2020.Available at:. https://www.triesteallnews.it/2020/03/14/coronavirus-willtocilizumab- be-the-drug-of-hope/
[36]
Venkiteshwaran, A. Tocilizumab. MAbs, 2009, 1(5), 432-438.
[http://dx.doi.org/10.4161/mabs.1.5.9497] [PMID: 20065633]
[37]
REUTERS (World News); China approves use of Roche drug in battle against coronavirus complications, 2019.Available at:. https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-rochearthritis- drug-for-coronavirus-patients-idUSKBN20R0LF
[38]
Kadam, R.U.; Wilson, I.A. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc. Natl. Acad. Sci. USA, 2017, 114(2), 206-214.
[http://dx.doi.org/10.1073/pnas.1617020114] [PMID: 28003465]
[39]
South China Morning Post; Notice on last positive results in China with combination therapies with antiviral drugs used against, 2019.Available at:. https://www.scmp.com/ news/china/society/article/3048993/chinese-officials-saypriority-stop-mild-coronavirus-cases


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 27
Year: 2020
Page: [4536 - 4541]
Pages: 6
DOI: 10.2174/0929867327666200416131117

Article Metrics

PDF: 512
HTML: 49
PRC: 6



Related Article(s)