4.7 Review

Comprehensive Consensus Analysis of SARS-CoV-2 Drug Repurposing Campaigns

Journal

JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 61, Issue 8, Pages 3771-3788

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.1c00384

Keywords

COVID-19; SARS-CoV-2; drug repurposing; chemical libraries; high-throughput screening; virtual screening; docking; main protease; spike protein

Funding

  1. Canadian Institutes of Health Research (CIHR), Canadian 2019 Novel Coronavirus (2019nCoV) Rapid Research grants [OV3-170631, VR3172639]
  2. CIHR [MFE-171324]
  3. Michael Smith Foundation for Health Research/VCHRI AMP
  4. VGH UBC Hospital Foundation [RT-2020-0408]
  5. Ermenegildo Zegna Foundation
  6. TELUS
  7. Teck Resources
  8. 625 Powell Street Foundation
  9. Tai Hung Fai Charitable Foundation
  10. Vancouver General Hospital Foundation

Ask authors/readers for more resources

The current COVID-19 pandemic has sparked widespread repurposing efforts to quickly identify treatments, but studies show significant variability in efficacy. Therefore, standardizing best practices, including the use of relevant cell lines, viral isolates, and validated screening protocols, is crucial. Furthermore, there is a focus on biochemical and virtual screening studies against SARS-CoV-2 targets, as well as consistent activity of repurposing candidates.
The current COVID-19 pandemic has elicited extensive repurposing efforts (both small and large scale) to rapidly identify COVID-19 treatments among approved drugs. Herein, we provide a literature review of large-scale SARS-CoV-2 antiviral drug repurposing efforts and highlight a marked lack of consistent potency reporting. This variability indicates the importance of standardizing best practices-including the use of relevant cell lines, viral isolates, and validated screening protocols. We further surveyed available biochemical and virtual screening studies against SARS-CoV-2 targets (Spike, ACE2, RdRp, PLpro, and M-pro) and discuss repurposing candidates exhibiting consistent activity across diverse, triaging assays and predictive models. Moreover, we examine repurposed drugs and their efficacy against COVID-19 and the outcomes of representative repurposed drugs in clinical trials. Finally, we propose a drug repurposing pipeline to encourage the implementation of standard methods to fast-track the discovery of candidates and to ensure reproducible results.

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