Screening a Library of FDA-Approved and Bioactive Compounds for Antiviral Activity against SARS-CoV-2
Biering SB, Van Dis E, Wehri E...Ott M, Murthy N, Nomura DK, Schaletzky J and Stanley SA. ACS Infectious Diseases(2021)
We are developing small-molecule therapeutics that will inhibit key COVID-19 (SARS-CoV-2) proteins.
The coronavirus genome encodes several proteins that are promising targets for drug development. We will target two classes of COVID-19 proteins, viral cysteine proteases and the ribosome-viral-polypeptide complex.
Our goal is to target COVID-19 by (1) developing cysteine-reactive covalent inhibitors against 3CLpro and PLpro through chemoproteomics-enabled covalent ligand screening approaches, and (2) developing small-molecules that selectively stall translation of viral proteins by inducing the ribosome to stall in a sequence-dependent manner of the nascent chain within the ribosomal exit tunnel. In addition, we are interested in identifying inhibitors for RdRp. RdRp synthesizes a full-length negative-strand RNA template to be used by RdRp to make more viral genomic RNA.
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