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A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
David E Gordon1,2,3,4, Gwendolyn M Jang1,2,3,4, Mehdi Bouhaddou1,2,3,4
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
Nature
|May 1, 2020
Summary
Researchers identified 332 protein-protein interactions between SARS-CoV-2 and human cells. They found 69 compounds targeting 66 druggable human proteins, with two drug types showing antiviral activity against COVID-19.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic with no approved treatments or vaccines.
- Understanding SARS-CoV-2's cellular infection mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To identify host-pathogen interactions between SARS-CoV-2 and human proteins.
- To discover potential drug targets and antiviral compounds for COVID-19 treatment.
Main Methods:
- Cloned, tagged, and expressed 26 SARS-CoV-2 proteins in human cells.
- Utilized affinity-purification mass spectrometry to identify protein-protein interactions.
- Screened identified compounds for antiviral activity in viral assays.
Main Results:
- Identified 332 high-confidence SARS-CoV-2-human protein-protein interactions.
- Found 66 druggable human proteins targeted by 69 compounds, including FDA-approved drugs.
- Discovered antiviral activity in mRNA translation inhibitors and sigma receptor modulators.
Conclusions:
- Host-targeting agents show promise for COVID-19 therapy.
- Combination therapies involving host-factor-targeting agents could be a viable treatment strategy.
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