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Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.
Lo, Ho Sing; Hui, Kenrie Pui Yan; Lai, Hei-Ming; He, Xu; Khan, Khadija Shahed; Kaur, Simranjeet; Huang, Junzhe; Li, Zhongqi; Chan, Anthony K N; Cheung, Hayley Hei-Yin; Ng, Ka-Chun; Ho, John Chi Wang; Chen, Yu Wai; Ma, Bowen; Cheung, Peter Man-Hin; Shin, Donghyuk; Wang, Kaidao; Lee, Meng-Hsuan; Selisko, Barbara; Eydoux, Cecilia; Guillemot, Jean-Claude; Canard, Bruno; Wu, Kuen-Phon; Liang, Po-Huang; Dikic, Ivan; Zuo, Zhong; Chan, Francis K L; Hui, David S C; Mok, Vincent C T; Wong, Kam-Bo; Mok, Chris Ka Pun; Ko, Ho; Aik, Wei Shen; Chan, Michael Chi Wai; Ng, Wai-Lung.
  • Lo HS; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Hui KPY; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  • Lai HM; Centre for Immunology and Infection (C2I), Hong Kong Science Park, Hong Kong, SAR, China.
  • He X; Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Khan KS; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Kaur S; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Huang J; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Li Z; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Chan AKN; Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
  • Cheung HH; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Ng KC; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Ho JCW; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Chen YW; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Ma B; Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, California 91010, United States.
  • Cheung PM; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Shin D; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  • Wang K; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  • Lee MH; Department of Applied Biology and Chemical Technology and the State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.
  • Selisko B; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Eydoux C; School of Public Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Guillemot JC; Buchmann Institute for Molecular Life Sciences, Goethe University, 60323 Frankfurt am Main, Germany.
  • Canard B; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
  • Wu KP; Protein Production Department, GenScript Biotech Corporation, Nanjing, Jiangsu Province 211100, China.
  • Liang PH; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
  • Dikic I; Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.
  • Zuo Z; Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.
  • Chan FKL; Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.
  • Hui DSC; Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.
  • Mok VCT; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
  • Wong KB; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.
  • Mok CKP; Buchmann Institute for Molecular Life Sciences, Goethe University, 60323 Frankfurt am Main, Germany.
  • Ko H; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Aik WS; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Chan MCW; Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Ng WL; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
ACS Cent Sci ; 7(5): 792-802, 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1225483
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.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: ACS Cent Sci Year: 2021 Document Type: Article Affiliation country: Acscentsci.0c01186

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: ACS Cent Sci Year: 2021 Document Type: Article Affiliation country: Acscentsci.0c01186