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SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development
Nicholas Murgolo1, Alex G Therien2, Bonnie Howell3
1Department of Genetics and Pharmacogenomics, Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
Plos Pathogens
|February 17, 2021
Summary
Drug repurposing screens show promise for COVID-19 treatments, but using non-human cell lines raises questions about real-world effectiveness. Further research is needed to develop better in vitro models for drug discovery.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic with a wide spectrum of disease severity.
- Current FDA-approved treatments for COVID-19 are limited, with remdesivir being the only one.
- Early therapeutic strategies have focused on drug repurposing to find existing compounds with antiviral activity against SARS-CoV-2.
Purpose of the Study:
- To discuss the key molecular and cellular interactions in SARS-CoV-2 infection.
- To provide a framework for developing an appropriate in vitro toolbox for drug discovery.
- To address the limitations of current drug repurposing screens using non-human cell lines.
Main Methods:
- Review of current understanding of SARS-CoV-2 molecular and cellular interactions.
- Analysis of drug repurposing screens for antiviral compounds.
- Evaluation of the physiological and pathological relevance of in vitro models.
Main Results:
- Drug repurposing screens have identified potential antiviral compounds.
- The use of non-human immortalized cell lines presents challenges in predicting clinical efficacy.
- There is a need for more physiologically relevant in vitro models.
Conclusions:
- Understanding SARS-CoV-2 infection mechanisms is crucial for effective drug development.
- Improved in vitro models are essential to support current and future drug discovery efforts for COVID-19.
- Further research should focus on validating drug candidates in more relevant cellular systems.
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