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SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug

Thuy X Pham1, Trang T X Huynh1, Jiwon Choi2

  • 1Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, South Korea.

Journal of Virology
|December 5, 2023
PubMed
Abstract

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses host RAD51 for replication. RAD51 inhibitors show antiviral activity, suggesting RAD51 as a potential drug target for COVID-19 treatment.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Viruses evolve to enhance host propagation.
  • Host factors are crucial for viral replication and pathogenesis.
  • Understanding host-viral interactions is key to developing therapeutics.

Purpose of the Study:

  • To investigate the role of host RAD51 in SARS-CoV-2 replication.
  • To evaluate RAD51 inhibitors as potential antiviral agents against SARS-CoV-2.
  • To identify novel host-based drug targets for COVID-19.

Main Methods:

  • Gene silencing to assess RAD51 function in SARS-CoV-2 propagation.
  • Immunofluorescence to visualize colocalization of viral RNA and RAD51.
  • Antiviral assays to test RAD51 inhibitors against SARS-CoV-2.
  • Molecular docking to elucidate the mechanism of RAD51 inhibition.

Main Results:

  • RAD51 is utilized by SARS-CoV-2 for replication.
  • Silencing RAD51 significantly impaired SARS-CoV-2 propagation.
  • Viral RNA and RAD51 colocalized in infected cell cytoplasm, forming a potential replication complex.
  • RAD51 inhibitors demonstrated antiviral activity against SARS-CoV-2 Wuhan strain and variants.
  • Molecular docking indicated inhibitors disrupt RAD51 dimerization, hindering viral propagation.

Conclusions:

  • Host RAD51 is essential for SARS-CoV-2 replication.
  • RAD51 inhibitors represent a promising therapeutic strategy against SARS-CoV-2 and its variants.
  • Targeting host factor RAD51 offers a novel approach for COVID-19 treatment.
Keywords:
COVID-19RAD51RAD51 inhibitorSARS-CoV-2therapeutic agent

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