Accelerating antiviral drug discovery: lessons from COVID-19

Journal article : Review

During the coronavirus disease 2019 (COVID-19) pandemic, a wave of rapid and collaborative drug discovery efforts took place in academia and industry, culminating in several therapeutics being discovered, approved and deployed in a 2-year time frame. This article summarizes the collective experience of several pharmaceutical companies and academic collaborations that were active in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline our opinions and experiences on key stages in the small-molecule drug discovery process: target selection, medicinal chemistry, antiviral assays, animal efficacy and attempts to pre-empt resistance. We propose strategies that could accelerate future efforts and argue that a key bottleneck is the lack of quality chemical probes around understudied viral targets, which would serve as a starting point for drug discovery. Considering the small size of the viral proteome, comprehensively building an arsenal of probes for proteins in viruses of pandemic concern is a worthwhile and tractable challenge for the community.

Authors: von Delft, A; Hall, MD; Kwong, AD; Purcell, LA; Saikatendu, KS

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Reviews Drug Discovery
• Volume: 22
• Issue: 7
• Pages: 585-603
• Publication date: 2023-05-12
• Acceptance date: 2023-04-04
• DOI: 10.1038/s41573-023-00692-8
• EISSN: 1474-1784
• ISSN: 1474-1776
• Pmid: 37173515
• Language: English
• Keywords: animals; FFR; pandemics; COVID-19; SARS-CoV-2; drug discovery; antiviral agents
• Subtype: Review