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

Ho Sing Lo, Kenrie Pui Yan Hui, Hei Ming 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, Donghyuk Shin, Kaidao Wang, Meng Hsuan Lee, Barbara Selisko, Cecilia EydouxJean 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, Chris Ka Pun Mok, Ho Ko, Wei Shen Aik, Michael Chi Wai Chan, Wai Lung Ng

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28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)792-802
Number of pages11
JournalACS Central Science
Issue number5
Publication statusPublished - 2021 May 26

Bibliographical note

Funding Information:
W.L.N. acknowledges funding support from CUHK (“Improvement on competitiveness in hiring new faculties funding scheme”, a seed fund from the Faculty of Medicine and a PIEF grant [Ph2/COVID/19]) and the Croucher Foundation (start-up fund). M.C.W.C. acknowledges funding support by the Theme Based Research Scheme [T11-322 712/19-N], Research Grants Council, Hong Kong SAR, and the US National Institute of Allergy and Infectious Diseases (NIAID) under the Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400006C]. W.S.A. acknowledges HKBU’s funding support through the Tier2 Start-up Grant (RC-SGT2/18-19/SCI/003). D.S. acknowledges the funding support of National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (no. 2021R1C1C1003961). The work of the BC group was supported by the Fondation pour la Recherche Médicale (Aide aux équipes), the SCORE project H2020 SC1-PHE-Coronavirus-2020 (grant #101003627) and the CARE project (grant #101005077) within IMI2 Europe’s partnership for health.

Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)


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