A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

Sci Rep. 2016 Feb 25;6:22008. doi: 10.1038/srep22008.

Abstract

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Endosomes / virology
  • Influenza A virus / drug effects
  • Influenza A virus / physiology
  • Inhibitory Concentration 50
  • Mice
  • Microbial Sensitivity Tests
  • Middle East Respiratory Syndrome Coronavirus / drug effects
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Peptide Fragments / pharmacology
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Protein Binding
  • SARS Virus / drug effects
  • Viral Envelope Proteins / metabolism
  • Viral Load
  • beta-Defensins / chemistry

Substances

  • Antiviral Agents
  • Defb4 protein, mouse
  • Peptide Fragments
  • Peptides
  • Viral Envelope Proteins
  • beta-Defensins