ACS central science · 2021
Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.
СтатьяНазвание и аннотация: Перевод в очереди
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Lo Ho Sing, Hui Kenrie Pui Yan, Lai Hei-Ming, He Xu, Khan Khadija Shahed, Kaur Simranjeet, Huang Junzhe, Li Zhongqi, Chan Anthony K N, Cheung Hayley Hei-Yin, Ng Ka-Chun, Ho John Chi Wang, Chen Yu Wai, Ma Bowen, Cheung Peter Man-Hin, Shin Donghyuk, Wang Kaidao, Lee Meng-Hsuan, Selisko Barbara, Eydoux Cecilia, Guillemot Jean-Claude, Canard Bruno, Wu Kuen-Phon, Liang Po-Huang, Dikic Ivan, Zuo Zhong, Chan Francis K L, Hui David S C, Mok Vincent C T, Wong Kam-Bo, Mok Chris Ka Pun, Ko Ho, Aik Wei Shen, Chan Michael Chi Wai, Ng Wai-Lung
Аннотация
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir not only inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp) but also modulates host immune responses. Our results thus reveal the possible anti-SARS-CoV-2 mechanism of simeprevir and highlight the translational potential of optimizing simeprevir as a therapeutic agent for managing COVID-19 and future outbreaks of CoV.