Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.

ABSTRACT: Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host. Despite being a promising antiviral target, it has been difficult to develop small-molecule inhibitors that target the EndoU active site. We generated nsp15 mutants of the coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mouse hepatitis virus (MHV)-A59 and identified conserved residues within the amino-terminal domain that are required for EndoU activity.

SUBMITTER: Evdokimova M 

PROVIDER: S-EPMC11912388 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature