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Nat Commun . A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2

tetano

Editor, Senior Moderator
Nat Commun


. 2020 Aug 25;11(1):4252.
doi: 10.1038/s41467-020-17986-9.
A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2


Hanjun Zhao[SUP] 1 2 3 [/SUP], Kelvin K W To[SUP] 1 2 3 4 5 [/SUP], Kong-**** Sze[SUP] 1 2 [/SUP], Timothy Tin-Mong Yung[SUP] 2 3 [/SUP], Mingjie Bian[SUP] 6 [/SUP], Hoiyan Lam[SUP] 2 3 [/SUP], Man Lung Yeung[SUP] 1 2 3 5 [/SUP], Cun Li[SUP] 2 3 [/SUP], Hin Chu[SUP] 1 2 3 [/SUP], Kwok-Yung Yuen[SUP] 7 8 9 10 11 [/SUP]



Affiliations

Abstract

The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses.
 
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