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Updated: Oct 11, 2025

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target

Gergely Rona1,2,3, Andras Zeke1,2,4, Bearach Miwatani-Minter1,2

  • 1Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, 10016, USA.

Cell Death and Differentiation
|December 4, 2021
PubMed

Insights

Developing pan-coronavirus antivirals is crucial. Researchers identified compounds inhibiting the NSP14-NSP10 complex, enhancing remdesivir

Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • The COVID-19 pandemic underscores the threat of zoonotic coronaviruses.
  • Existing antivirals like remdesivir are hindered by viral proofreading mechanisms.

Purpose of the Study:

  • To identify inhibitors of the SARS-CoV-2 NSP14-NSP10 complex.
  • To enhance the efficacy of existing antiviral therapies.

Main Methods:

  • Development of a novel assay for screening.
  • In silico modeling and virtual screening.
  • In vitro inhibition assays and cellular replication studies.

Main Results:

  • Identified inhibitors of the NSP14-NSP10 exonuclease complex.
  • Sofalcone demonstrated inhibition of SARS-CoV-2, SARS-CoV, and MERS-CoV exonuclease activity.
  • Sofalcone synergistically enhanced remdesivir's antiviral effect and suppressed viral replication.

Conclusions:

  • The NSP14-NSP10 complex is a viable therapeutic target for pan-coronavirus drug development.
  • Inhibiting viral proofreading mechanisms can restore antiviral potency.
  • This approach offers a strategy for developing broad-spectrum coronavirus therapeutics.

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