期刊
EMERGING MICROBES & INFECTIONS
卷 11, 期 1, 页码 926-937出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2022.2051753
关键词
Antiviral peptide; Delta variant; fusion; influenza virus; Omicron variant; SARS-CoV-2
资金
- Health@InnoHK (Centre for Virology, Vaccinology and Therapeutics), Innovation and Technology Commission
- Government of the Hong Kong Special Administrative Region Theme-Based Research Scheme of the Research Grants Council [T11-709/21-N]
- National Key Research and Development Programme on Public Security Risk Prevention and Control Emergency Project, Emergency Key Program of Guangzhou Laboratory [EKPG22-01]
- Health and Medical Research Fund
- Food and Health Bureau
- Government of the Hong Kong Special Administrative Region [COVID1903010-Project 13]
- National Program on Key Research Project of China [2020YFA0707500, 2020YFA0707504]
- National Key R&D Program of China [2017YFA0503900]
- National Natural Science Foundation of China [32071270]
- Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases
- Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government
- Richard Yu and Carol Yu, Michael Seak-Kan Tong, May Tam Mak Mei Yin, the Shaw Foundation Hong Kong, Providence Foundation Limited
- Lee Wan Keung Charity Foundation Limited
- Respiratory Viral Research Foundation Limited
- Hui Ming
- Hui Hoy and Chow Sin Lan Charity Fund Limited
- Chan Yin Chuen Memorial Charitable Foundation
- Marina Man-Wai Lee
The study demonstrates a frog-defensin-derived basic peptide (FBP) as a broad-spectrum inhibitor against influenza virus and SARS-CoV-2 by blocking viral entry and fusion to inhibit virus replication in vivo.
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.
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