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Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir

2021; American Chemical Society; Volume: 7; Issue: 5 Linguagem: Inglês

10.1021/acscentsci.0c01186

2374-7951

Ho Sing Lo, Kenrie Pui Yan Hui, H. M. Lai, Xu He, Khadija Shahed Khan, Simranjeet Kaur, Junzhe Huang, Zhongqi Li, Anthony K. N. Chan, Hayley Hei-Yin Cheung, Ka‐Chun Ng, John Chi Wang Ho, Yu Wai Chen, Bowen Ma, Peter Man-Hin Cheung, Dong Hyuk Shin, Kaidao Wang, Meng-Hsuan Lee, Barbara Selisko, Cécilia Eydoux, Jean-Claude Guillemot, Bruno Canard, Kuen‐Phon Wu, Po‐Huang Liang, Ivan Đikić, Zhong Zuo, Francis K.L. Chan, David S.C. Hui, Vincent Mok, Kam‐Bo Wong, Chris Ka Pun Mok, Ho Ko, Wei Shen Aik, Mcw Chan, Wai‐Lung Ng,

COVID-19 Clinical Research Studies

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.