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Published anti-SARS-CoV-2 in vitro hits share common mechanisms of action that synergize with antivirals.
- Source :
- Briefings in Bioinformatics; Nov2021, Vol. 22 Issue 6, p1-11, 11p
- Publication Year :
- 2021
-
Abstract
- The global efforts in the past year have led to the discovery of nearly 200 drug repurposing candidates for COVID-19. Gaining more insights into their mechanisms of action could facilitate a better understanding of infection and the development of therapeutics. Leveraging large-scale drug-induced gene expression profiles, we found 36% of the active compounds regulate genes related to cholesterol homeostasis and microtubule cytoskeleton organization. Following bioinformatics analyses revealed that the expression of these genes is associated with COVID-19 patient severity and has predictive power on anti-SARS-CoV-2 efficacy in vitro. Monensin, a top new compound that regulates these genes, was further confirmed as an inhibitor of SARS-CoV-2 replication in Vero-E6 cells. Interestingly, drugs co-targeting cholesterol homeostasis and microtubule cytoskeleton organization processes more likely present a synergistic effect with antivirals. Therefore, potential therapeutics could be centered around combinations of targeting these processes and viral proteins. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14675463
- Volume :
- 22
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Briefings in Bioinformatics
- Publication Type :
- Academic Journal
- Accession number :
- 154512620
- Full Text :
- https://doi.org/10.1093/bib/bbab249