SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVID-19

J Virol. 2023 Dec 21;97(12):e0173723. doi: 10.1128/jvi.01737-23. Epub 2023 Dec 5.


Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.

Keywords: COVID-19; RAD51; RAD51 inhibitor; SARS-CoV-2; therapeutic agent.

MeSH terms

  • COVID-19* / metabolism
  • COVID-19* / virology
  • Host-Pathogen Interactions
  • Humans
  • Molecular Docking Simulation
  • RNA, Viral
  • Rad51 Recombinase / antagonists & inhibitors
  • Rad51 Recombinase / metabolism
  • SARS-CoV-2* / physiology


  • RAD51 protein, human
  • Rad51 Recombinase
  • RNA, Viral