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Recently, customers who purchased the ChemFaces compound screening library published an article in the top journal Cell Death & Differentiation: The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target.
This article is dedicated to the compound library screening of SARS-CoV-2 pandemic, in order to find valuable compounds for further research and development.
Cell Death & Differentiation: (IF 2021: 15.828)
Copyright: Nature
Society: https://www.nature.com/articles/s41418-021-00900-1#auth-Michele-Pagano
Abstract
The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone, both inhibits the exonuclease activity of SARS-CoV-2, SARS-CoV, and MERS-CoV in vitro, and synergistically enhances the antiviral effect of remdesivir, suppressing the replication of SARS-CoV-2 and the related human coronavirus OC43. The validation of top hits from our primary screenings using cellular systems provides proof-of-concept for the NSP14 complex as a therapeutic target.