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 5:e0173723. doi: 10.1128/jvi.01737-23.
- 1. Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, South Korea.
- 2. College of Pharmacy, Dongduk Women's University, Seoul, South Korea.
- 3. Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, South Korea.
- 4. Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan, South Korea.
- 5. Ilsong Institute of Life Science, Hallym University, Seoul, South Korea.
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.