Binding of SARS-CoV-1/2 NSP1 to DNA Polymerase α-Primase Inhibits DNA Replication through Reduction of Interaction between DNA and DNA Polymerase α-Primase.

ABSTRACT: A comprehensive understanding of the atomic level mechanism governing the binding nonstructural protein 1 of SARS-CoV-1 (SARS-CoV-1 NSP1) and SARS-CoV-2 (SARS-CoV-2 NSP1) to Pol α-primase is important to advance the development of small molecule inhibitors for the treatment COVID-19. In this study, we use both all-atom steered molecular dynamics (all-atom SMD) and coarse-grained umbrella sampling (coarse-grained US) simulations to assess the binding affinity of SARS-CoV-1 NSP1 and SARS-CoV-2 NSP1 to Pol α-primase. Our all-atom SMD and coarse-grained US simulations consistently indicate that SARS-CoV-2 NSP1 exhibits stronger affinity for Pol α-primase compared to SARS-CoV-1 NSP1, implying that SARS-CoV-2 poses a greater risk than SARS-CoV-1 in impeding DNA replication for DNA synthesis. Thr

SUBMITTER: Nguyen HV 

PROVIDER: S-EPMC12344767 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature