Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3.

ABSTRACT: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and in

SUBMITTER: Virdi RS 

PROVIDER: S-EPMC7684785 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature