An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses

Immunity. 2017 Apr 18;46(4):587-595. doi: 10.1016/j.immuni.2017.03.018.

Abstract

Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses. Using electron microscopy, we showed that this peptide physically destroyed influenza virions. It also protected naive mice from lethal influenza infection. Urumin represents a unique class of anti-influenza virucide that specifically targets the hemagglutinin stalk region, similar to targeting of antibodies induced by universal influenza vaccines. Urumin therefore has the potential to contribute to first-line anti-viral treatments during influenza outbreaks.

Keywords: antiviral; host defense peptide; influenza; innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amphibian Proteins / immunology
  • Amphibian Proteins / pharmacology*
  • Animals
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology
  • Dogs
  • Dose-Response Relationship, Drug
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / immunology
  • Influenza A virus / metabolism
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Peptides / immunology
  • Peptides / pharmacology*
  • Ranidae / metabolism
  • Survival Analysis
  • Treatment Outcome
  • Virion / drug effects
  • Virion / immunology
  • Virion / metabolism

Substances

  • Amphibian Proteins
  • Antiviral Agents
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Peptides
  • hemagglutinin, human influenza A virus
  • urumin peptide, Hydrophylax bahuvistara