Journal
ACS CENTRAL SCIENCE
Volume 7, Issue 5, Pages 792-802Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.0c01186
Keywords
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Funding
- CUHK (Improvement on competitiveness in hiring new faculties funding scheme)
- CUHK (Faculty of Medicine)
- Croucher Foundation
- Theme Based Research Scheme [T11-322 712/19-N]
- Research Grants Council, Hong Kong SAR
- US National Institute of Allergy and Infectious Diseases (NIAID) under the Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400006C]
- HKBU through Tier2 Start-up Grant [RC-SGT2/1819/SCI/003]
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2021R1C1C1003961]
- Fondation pour la Recherche Medicale (Aide aux equipes)
- SCORE project H2020 SC1-PHE-Coronavirus-2020 [101003627]
- CARE project within IMI2 Europe's partnership for health [101005077]
- CUHK (PIEF grant) [Ph2/COVID/19]
- National Research Foundation of Korea [2021R1C1C1003961] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Simeprevir has been identified as a promising repurposable drug for treating COVID-19, reducing SARS-CoV-2 viral load significantly and synergizing with remdesivir in vitro. Additionally, Simeprevir inhibits key viral proteins and modulates host immune responses.
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 (M-pro) 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.
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