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Structural biology of SARS-CoV-2 endoribonuclease NendoU (nsp15)

DOI: 10.1080/0889311X.2022.2065270 DOI Help

Authors: Sam Horrell (Diamond Light Source) , Gianluca Santoni (European Synchrotron Radiation Facility) , Andrea Thorn (Universität Hamburg)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Crystallography Reviews , VOL 11 , PAGES 1 - 17

State: Published (Approved)
Published: June 2022

Abstract: The SARS-CoV-2’s endoribonuclease (NendoU) nsp15, is an Mn2+ dependent endoribonuclease specific to uridylate that SARS-CoV-2 uses to avoid the innate immune response by managing the stray RNA generated during replication. As of the writing of this review 20 structures of SARS-CoV-2 nsp15 have been deposited into the PDB, largely solved using X-ray crystallography and some through Cryo-EM. These structures show that an nsp15 monomer consist of three conserved domains, the N-terminal oligomerization domain, the middle domain, and the catalytic NendoU domain. Enzymatically active nsp15 forms a hexamer through a dimer of trimers (point group 32), whose assembly is facilitated by the oligomerization domain. This review summarises the structural and functional information gained from SARs-CoV-2, SARs-CoV and MERS-CoV nsp15 structures, compiles the current structure-based drug design efforts, and complementary knowledge with a view to provide a clear starting point for downstream structure users interested in studying nsp15 as a novel drug target to treat COVID-19.

Journal Keywords: COVID-19; SARS-CoV-2; nsp15; endoribonuclease; RNA; computational drug design; structure based drug design

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine

Technical Areas:

Added On: 15/07/2022 09:16

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags: