Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electr

SUBMITTER: Godoy AS 

PROVIDER: S-EPMC10250223 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature