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

  • Nat Commun. 2020 Aug 25;11(1):4252. doi: 10.1038/s41467-020-17986-9.
Hanjun Zhao  #  1  2  3 ,  Kelvin K W To  #  1  2  3  4  5 ,  Kong-Hung Sze  #  1  2 ,  Timothy Tin-Mong Yung  2  3 ,  Mingjie Bian  6 ,  Hoiyan Lam  2  3 ,  Man Lung Yeung  1  2  3  5 ,  Cun Li  2  3 ,  Hin Chu  1  2  3 ,  Kwok-Yung Yuen  7  8  9  10  11
Affiliations
  • 1. Li Ka Shing Faculty of Medicine, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 2. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 3. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, China.
  • 4. Li Ka Shing Faculty of Medicine, Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 5. The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China.
  • 6. School of Life Science, Anhui Normal University, Wuhu, Anhui, China.
  • 7. Li Ka Shing Faculty of Medicine, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. [email protected].
  • 8. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. [email protected].
  • 9. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, China. [email protected].
  • 10. Li Ka Shing Faculty of Medicine, Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. [email protected].
  • 11. The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China. [email protected].
  • # Contributed equally.
PMID: 32843628 DOI: 10.1038/s41467-020-17986-9
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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