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Physical Sciences › Computer Science › Computational Theory and Mathematics
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
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Conflicts of Interest
Identified Weaknesses
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Paper Summary
Paperzilla title
Stealing from the Virus' Playbook: Unmasking COVID-19's Host Helpers and Drugging Them!
This study mapped 332 SARS-CoV-2-human protein interactions, revealing key pathways hijacked by the virus, including translation, vesicle trafficking, and innate immunity. This led to the identification of 69 existing compounds targeting these interactions, with some showing promising antiviral activity in vitro, particularly translation inhibitors and sigma receptor ligands.
Possible Conflicts of Interest
The Krogan laboratory has received research support from Vir Biotechnology and F. Hoffmann-La Roche. K.M.S. has consulting agreements with several pharmaceutical companies. J.T. is a cofounder and shareholder of several biotech companies. J.T. and P.P.S. are listed as inventors on a patent application related to PS3061. D.R. is a shareholder of and advisor to EFFECTOR Therapeutics. C.S.C. is a co-founder of two bioscience companies and receives support from ShangPharma/ChemPartners. A.A. has various affiliations and financial interests in biotech companies.
Identified Weaknesses
Cell line used for protein interaction mapping
The study relies on HEK-293T/17 cells for the protein interaction mapping, which are not the primary physiological site of infection (lung tissue). While the interacting proteins were found to be highly expressed in lung tissue, using a more relevant cell type would strengthen the findings.
Limited drug screening
The study identifies potential drug targets but only screens a subset in multiple viral assays. More comprehensive testing in relevant in vitro and in vivo models is needed to validate the antiviral activity and assess efficacy.
Cytostatic effects of some compounds
The antiviral activity of some compounds, like zotatifin, appears to stem from cytostatic effects observed in Vero E6 cells. This raises concerns about the potential for toxicity and the need to carefully differentiate between true antiviral activity and non-specific effects on cell growth.
Unclear mechanism of sigma receptor ligands
The study highlights the potential of sigma receptor ligands as antivirals, but the mechanism of action remains unclear. Further investigation is needed to determine which receptor (sigma-1 or sigma-2) is responsible and to understand the underlying molecular mechanisms.
Rating Explanation
This study makes a significant contribution to our understanding of SARS-CoV-2 biology and identifies potential therapeutic targets. The systematic mapping of protein-protein interactions and the drug screening provide valuable leads for drug repurposing and development. However, the reliance on a non-lung cell line and limited in vivo validation are notable limitations. The declared conflicts of interest are also a factor to consider.
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Original Title:
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
File Name:
s41586-020-2286-9.pdf
[download]
File Size:
10.53 MB
Uploaded:
July 14, 2025 at 10:36 AM
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