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Altered host protease determinants for SARS-CoV-2 Omicron.
Chan, Jasper Fuk-Woo; Huang, Xiner; Hu, Bingjie; Chai, Yue; Shi, Hongyu; Zhu, Tianrenzheng; Yuen, Terrence Tsz-Tai; Liu, Yuanchen; Liu, Huan; Shi, Jialu; Wen, Lei; Shuai, Huiping; Hou, Yuxin; Yoon, Chaemin; Cai, Jian-Piao; Zhang, Anna Jinxia; Zhou, Jie; Yin, Feifei; Yuan, Shuofeng; Zhang, Bao-Zhong; Brindley, Melinda A; Shi, Zheng-Li; Yuen, Kwok-Yung; Chu, Hin.
  • Chan JF; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Huang X; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.
  • Hu B; Centre for Virology, Vaccinology, and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China.
  • Chai Y; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong, Special Administrative Region, People's Republic of China.
  • Shi H; Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan Province, People's Republic of China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrat
  • Zhu T; Guangzhou Laboratory, Guangdong Province, China.
  • Yuen TT; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Liu Y; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Liu H; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Shi J; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
  • Wen L; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Shuai H; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Hou Y; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Yoon C; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Cai JP; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Zhang AJ; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Zhou J; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Yin F; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Yuan S; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Zhang BZ; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Brindley MA; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Shi ZL; Centre for Virology, Vaccinology, and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China.
  • Yuen KY; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology and Carol Yu Centre for Infection, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Chu H; Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan Province, People's Republic of China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrat
Sci Adv ; 9(3): eadd3867, 2023 Jan 20.
Article in English | MEDLINE | ID: covidwho-2239636
ABSTRACT
Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Sci Adv Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Sci Adv Year: 2023 Document Type: Article