Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies

被引:117
作者
Singh, Awadhesh Kumar [1 ]
Singh, Akriti [2 ]
Singh, Ritu [3 ]
Misra, Anoop [4 ]
机构
[1] GD Hosp & Diabet Inst, Diabet & Endocrinol, Kolkata, W Bengal, India
[2] Coll Med & JNM Hosp, Nadia, W Bengal, India
[3] GD Hosp & Diabet Inst, Gynaecol & Obstet, Kolkata, W Bengal, India
[4] Fortis C DOC Hosp Diabet & Allied Sci, New Delhi, India
基金
美国国家卫生研究院;
关键词
Remdesivir; COVID-19; SARS-Co-V-2; Clinical outcome; Mortality; RESPIRATORY SYNDROME CORONAVIRUS; SARS; REPLICATION; INHIBITION; EFFICACY; GS-5734;
D O I
10.1016/j.dsx.2020.05.018
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background & aims: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. Methods: We systematically searched the PubMed, ChnicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as "Remdesivir" or 'GS-5734" AND "COVID-19" or "SARS-CoV-2" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. Results: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. Conclusions: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials. (C) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:641 / 648
页数:8
相关论文
共 44 条
[1]   Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease [J].
Agostini, Maria L. ;
Andres, Erica L. ;
Sims, Amy C. ;
Graham, Rachel L. ;
Sheahan, Timothy P. ;
Lu, Xiaotao ;
Smith, Everett Clinton ;
Case, James Brett ;
Feng, Joy Y. ;
Jordan, Robert ;
Ray, Adrian S. ;
Cihlar, Tomas ;
Siegel, Dustin ;
Mackman, Richard L. ;
Clarke, Michael O. ;
Baric, Ralph S. ;
Denison, Mark R. .
MBIO, 2018, 9 (02)
[2]  
Barbosa J, 2020, BIBLIO
[3]  
Barnard Dale L., 2006, Antiviral Chemistry & Chemotherapy, V17, P275
[4]   Covid-19 in Critically Ill Patients in the Seattle Region - Case Series [J].
Bhatraju, Pavan K. ;
Ghassemieh, Bijan J. ;
Nichols, Michelle ;
Kim, Richard ;
Jerome, Keith R. ;
Nalla, Arun K. ;
Greninger, Alexander L. ;
Pipavath, Sudhakar ;
Wurfel, Mark M. ;
Evans, Laura ;
Kritek, Patricia A. ;
West, T. Eoin ;
Luks, Andrew ;
Gerbino, Anthony ;
Dale, Chris R. ;
Goldman, Jason D. ;
O'Mahony, Shane ;
Mikacenic, Carmen .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (21) :2012-2022
[5]   Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities [J].
Biot, C ;
Daher, W ;
Chavain, N ;
Fandeur, T ;
Khalife, J ;
Dive, D ;
De Clercq, E .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (09) :2845-2849
[6]   Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection A Randomized Clinical Trial [J].
Borba, Mayla Gabriela Silva ;
Val, Fernando Fonseca Almeida ;
Sampaio, Vanderson Souza ;
Alexandre, Marcia Almeida Araujo ;
Melo, Gisely Cardoso ;
Brito, Marcelo ;
Mourao, Maria Paula Gomes ;
Brito-Sousa, Jose Diego ;
Baia-da-Silva, Djane ;
Guerra, Marcus Vinitius Farias ;
Hajjar, Ludhmila Abrahao ;
Pinto, Rosemary Costa ;
Balieiro, Antonio Alcirley Silva ;
Pacheco, Antonio Guilherme Fonseca ;
Santos, James Dean Oliveira, Jr. ;
Naveca, Felipe Gomes ;
Xavier, Mariana Simao ;
Siqueira, Andre Machado ;
Schwarzbold, Alexandre ;
Croda, Julio ;
Nogueira, Mauricio Lacerda ;
Romero, Gustavo Adolfo Sierra ;
Bassat, Quique ;
Fontes, Cor Jesus ;
Albuquerque, Bernardino Claudio ;
Daniel-Ribeiro, Claudio-Tadeu ;
Monteiro, Wuelton Marcelo ;
Lacerda, Marcus Vinicius Guimaraes .
JAMA NETWORK OPEN, 2020, 3 (04) :E208857
[7]   Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase [J].
Brown, Ariane J. ;
Won, John J. ;
Graham, Rachel L. ;
Dinnon, Kenneth H., III ;
Sims, Amy C. ;
Feng, Joy Y. ;
Cihlar, Tomas ;
Denison, Mark R. ;
Baric, Ralph S. ;
Sheahan, Timothy P. .
ANTIVIRAL RESEARCH, 2019, 169
[8]  
Cao B, 2020, NEW ENGL J MED, V382, P1787, DOI [10.1056/NEJMoa2001282, 10.1056/NEJMc2008043]
[9]   Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus [J].
Chan, Jasper F. W. ;
Chan, Kwok-Hung ;
Kao, Richard Y. T. ;
To, Kelvin K. W. ;
Zheng, Bo-Jian ;
Li, Clara P. Y. ;
Li, Patrick T. W. ;
Dai, Jun ;
Mok, Florence K. Y. ;
Chen, Honglin ;
Hayden, Frederick G. ;
Yuen, Kwok-Yung .
JOURNAL OF INFECTION, 2013, 67 (06) :606-616
[10]   In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds [J].
Chen, F ;
Chan, KH ;
Jiang, Y ;
Kao, RYT ;
Lu, HT ;
Fan, KW ;
Cheng, VCC ;
Tsui, WHW ;
Hung, IFN ;
Lee, TSW ;
Guan, Y ;
Peiris, JSM ;
Yuen, KY .
JOURNAL OF CLINICAL VIROLOGY, 2004, 31 (01) :69-75