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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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
Volume7
Issue number5
DOIs
Publication statusPublished - 26 May 2021

Scopus Subject Areas

  • Chemistry(all)
  • Chemical Engineering(all)

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