Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants.

Autor:	Zhao H; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Department of Microbiology, 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.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China., Meng X; Department of Microbiology, 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., Peng Z; Department of Microbiology, 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., Lam H; Department of Microbiology, 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 C; Department of Microbiology, 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 X; Department of Microbiology, 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., Chan JF; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Department of Microbiology, 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.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China.; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Guangzhou Laboratory, Guangzhou Province, China., Kao RYT; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Department of Microbiology, 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.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China., To KK; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Department of Microbiology, 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.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China.; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Guangzhou Laboratory, Guangzhou Province, China., Yuen KY; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Department of Microbiology, 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.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China.; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; Guangzhou Laboratory, Guangzhou Province, China.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2022 Dec; Vol. 11 (1), pp. 926-937.
DOI:	10.1080/22221751.2022.2051753
Abstrakt:	Pandemic influenza virus and SARS-CoV-2 vaiants have posed major global threats to public health. Broad-spectrum antivirals blocking viral entry can be an effective strategy for combating these viruses. Here, we demonstrate a frog-defensin-derived basic peptide (FBP), which broadly inhibits the influenza virus by binding to haemagglutinin so as to block low pH-induced HA-mediated fusion and antagonizes endosomal acidification to inhibit the influenza virus. Moreover, FBP can bind to the SARS-CoV-2 spike to block spike-mediated cell-cell fusion in 293T/ACE2 cells endocytosis. Omicron spike shows a weak cell-cell fusion mediated by TMPRSS2 in Calu3 cells, making the Omicron variant sensitive to endosomal inhibitors. In vivo studies show that FBP broadly inhibits the A(H1N1)pdm09 virus in mice and SARS-CoV-2 (HKU001a and Delta)in hamsters. Notably, FBP shows significant inhibition of Omicron variant replication even though it has a high number of mutations in spike. In conclusion, these results suggest that virus-targeting FBP with a high barrier to drug resistance can be an effective entry-fusion inhibitor against influenza virus and SARS-CoV-2 in vivo.
Databáze:	MEDLINE
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