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Accelerating antiviral drug discovery: lessons from COVID-19
Annette von Delft1,2, Matthew D Hall3, Ann D Kwong4
1Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Annette.vondelft@cmd.ox.ac.uk.
Nature Reviews. Drug Discovery
|May 12, 2023
Summary
Rapid drug discovery for coronavirus disease 2019 (COVID-19) yielded therapeutics quickly. A key bottleneck for future antiviral drug discovery is the lack of chemical probes for viral targets.
Area of Science:
- Virology
- Medicinal Chemistry
- Pharmaceutical Sciences
Background:
- The coronavirus disease 2019 (COVID-19) pandemic spurred unprecedented collaborative efforts in drug discovery.
- Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics were discovered, approved, and deployed within a two-year timeframe.
Purpose of the Study:
- To summarize collective experiences and opinions from academic and industrial collaborations in SARS-CoV-2 antiviral drug discovery.
- To propose strategies for accelerating future small-molecule antiviral drug discovery efforts.
Main Methods:
- Review of key stages in small-molecule drug discovery: target selection, medicinal chemistry, antiviral assays, and animal efficacy studies.
- Analysis of strategies for preempting antiviral resistance.
- Identification of bottlenecks in the drug discovery pipeline.
Main Results:
- The rapid development of COVID-19 therapeutics highlights the potential of collaborative drug discovery.
- A significant bottleneck identified is the scarcity of quality chemical probes for understudied viral targets.
- The small viral proteome presents a tractable challenge for developing a comprehensive probe arsenal.
Conclusions:
- Accelerating future antiviral drug discovery requires addressing the lack of chemical probes for viral targets.
- Building a community-wide arsenal of chemical probes for pandemic-relevant viruses is a crucial and achievable goal.
- Lessons learned from SARS-CoV-2 drug discovery can inform strategies for future viral threats.
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