Affordable Access

deepdyve-link
Publisher Website

The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target

Authors
  • Rona, Gergely
  • Zeke, Andras
  • Miwatani-Minter, Bearach
  • de Vries, Maren
  • Kaur, Ramanjit
  • Schinlever, Austin
  • Garcia, Sheena Faye
  • Goldberg, Hailey V.
  • Wang, Hui
  • Hinds, Thomas R.
  • Bailly, Fabrice
  • Zheng, Ning
  • Cotelle, Philippe
  • Desmaële, Didier
  • Landau, Nathaniel R.
  • Dittmann, Meike
  • Pagano, Michele
Type
Published Article
Journal
Cell Death and Differentiation
Publisher
Nature Publishing Group UK
Publication Date
Dec 03, 2021
Volume
29
Issue
2
Pages
285–292
Identifiers
DOI: 10.1038/s41418-021-00900-1
PMID: 34862481
PMCID: PMC8640510
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

Abstract

The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone, both inhibits the exonuclease activity of SARS-CoV-2, SARS-CoV, and MERS-CoV in vitro, and synergistically enhances the antiviral effect of remdesivir, suppressing the replication of SARS-CoV-2 and the related human coronavirus OC43. The validation of top hits from our primary screenings using cellular systems provides proof-of-concept for the NSP14 complex as a therapeutic target.

Report this publication

Statistics

Seen <100 times