CACHE Challenge #2: Targeting the RNA Site of the SARS-CoV-2 Helicase Nsp13.

ABSTRACT: A critical assessment of computational hit-finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening paired with advanced computational and machine learning methods to each predict up to 100 inhibitory ligands. Across all teams, 1957 compounds were predicted and were subsequently procured from commercial catalogs for biophysical assays. Of these compounds, 0.7% were confirmed to bind to Nsp13 in a surface plasmon resonance assay. The six best-performing computational workflows used fragment growing, active learning, or conventional virtual screenin

SUBMITTER: Herasymenko O 

PROVIDER: S-EPMC12323591 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature