A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
drug discovery/repurposing proteomics
Authors: Gordon et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3
Journal/ Pre-Print: bioRxiv
Key Words: pharmacological therapies, mass spectrometry, proteomics, host response
1. Identified 332 high confidence SARS-CoV-2-human protein-protein interactions.
2. Demonstrated that the interacting proteins were highly expressed or enriched in lung tissue
3. Identified 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds.
The authors expressed 26 strep-tagged SARS-CoV-2 proteins in the kidney-derived human cell line HEK293T, and used affinity-purified mass-spectrometry to identify 332 host proteins that interact with viral proteins. These host proteins fall in many pathways, including lipid modification and innate immunity. These interactions were not validated in lung cells, but the host proteins were overexpressed in lung relative to other tissues. 69 drugs, including 27 FDA-approved drugs, target these host proteins, though whether they would inhibit or encourage infection is unknown. The authors propose a genetic screen to test whether loss of these drug-targeted host proteins would impact viral infectivity.
Impact for SARS-CoV2/COVID19 research efforts
Understand the virology and/or cell biology of SARS-CoV2/COVID19
Inhibit of SARS-CoV2/COVID19 transmission
Treat of SARS-CoV2/COVID19 positive individuals
· In vitro study
Strengths and limitations of the paper
Novelty: Untargeted investigation of the host protein response to Sars-CoV-2
Standing in the field: Robust methods, however needs to be repeated or corroborated by other methods. E.g need to test the potential drug hits in cell culture.
Appropriate statistics: Not applicable
Viral model used: SARS-CoV-2 isolate 2019-nCoV/USA-WA1/2020
Translatability: Identification of an antiviral, but this requires testing in cell culture
Main limitations: The results show that there may be binding of these human proteins with Sars-CoV-2 proteins, but this needs to be repeated, and corroborated by other methods.