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J Virol . SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVI

tetano

Editor, Senior Moderator
J Virol


. 2023 Dec 5:e0173723.
doi: 10.1128/jvi.01737-23. Online ahead of print. SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVID-19

Thuy X Pham[SUP] 1 [/SUP], Trang T X Huynh[SUP] 1 [/SUP], Jiwon Choi[SUP] 2 [/SUP], Jae-Bong Lee[SUP] 3 [/SUP], Seok-Chan Park[SUP] 4 [/SUP], Bumseok Kim[SUP] 4 [/SUP], Yun-Sook Lim[SUP] 1 [/SUP], Soon B Hwang[SUP] 1 5 [/SUP]



Affiliations
Abstract

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.

 
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