Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir
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AbstractThe 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 inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients.
Acceptance Date26/05/2020
All Author(s) ListHo Sing Lo, Kenrie Pui Yan Hui, Hei-Ming Lai, 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, Donghyuk Shin, Kaidao Wang, Meng-Hsuan Lee, Barbara Selisko, Cecilia Eydoux, Jean-Claude Guillemot, Bruno Canard, Kuen-Phon Wu, Po-Huang Liang, Ivan Dikic, Zhong Zuo, Francis K. L. Chan, David S. C. Hui, Vincent C. T. Mok, Kam-Bo Wong, Ho Ko, Wei Shen Aik, Michael Chi Wai Chan, Wai-Lung Ng
Journal namebioRxiv
Year2020
Month9
Day3
eISSN2379-3708
LanguagesEnglish-United States

Last updated on 2021-26-07 at 23:51