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

Emerging Microbes and Infections

Xinxin Zhou¹  Zheng Peng¹  Xinjie Meng¹  Chuyuan Zhang¹  Hoiyan Lam¹  Kwok-Yung Yuen²  Kelvin Kai-Wang To²  Hanjun Zhao²  Richard Yi Tsun Kao²  Jasper Fuk-Woo Chan² 

[1] 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;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;

关键词: Antiviral peptide;    Delta variant;    fusion;    influenza virus;    Omicron variant;    SARS-CoV-2;   

DOI  :  10.1080/22221751.2022.2051753

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown