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. Here Zhao et al. report a promising broad-spectrum antiviral alkaline peptide—P9R—that is active against several respiratory, pH-dependent viruses, including Influenza and SARS-CoV-2. P9R interferes with virus internalization by binding to the virus and subsequent inhibition of endosomal acidification.
【저자키워드】 SARS-CoV-2, Drug discovery, antivirals, Influenza virus, 【초록키워드】 COVID-19, coronavirus, pandemic, Antiviral, SARS-CoV, Influenza, peptide, antiviral activity, virus, MERS-CoV, respiratory viruses, rhinovirus, respiratory virus, outbreak, mice, healthcare, Endosomal acidification, broad-spectrum antivirals, virus infection, disease, binding, highlight, combating, PROTECT, significantly, subsequent, inhibit, exhibited, provide, active against, interfere, cause, alkaline, drug-resistant, pH-dependent virus, pH-dependent viruses, 【제목키워드】 peptide, virus, respiratory virus,