Antiviral activity of formyl peptide receptor 2 antagonists against influenza viruses

Antiviral Res. 2017 Jul:143:252-261. doi: 10.1016/j.antiviral.2017.05.001. Epub 2017 May 5.

Abstract

Influenza viruses are one of the most important respiratory pathogens worldwide, causing both epidemic and pandemic infections. The aim of the study was to evaluate the effect of FPR2 antagonists PBP10 and BOC2 on influenza virus replication. We determined that these molecules exhibit antiviral effects against influenza A (H1N1, H3N2, H6N2) and B viruses. FPR2 antagonists used in combination with oseltamivir showed additive antiviral effects. Mechanistically, the antiviral effect of PBP10 and BOC2 is mediated through early inhibition of virus-induced ERK activation. Finally, our preclinical studies showed that FPR2 antagonists protected mice from lethal infections induced by influenza, both in a prophylactic and therapeutic manner. Thus, FPR2 antagonists might be explored for novel treatments against influenza.

Keywords: Antiviral; Formyl peptide receptor 2; Influenza virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells / drug effects
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Cell Survival
  • Dogs
  • Drug Combinations
  • Female
  • Gelsolin / administration & dosage
  • Gelsolin / antagonists & inhibitors*
  • Haplorhini
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H3N2 Subtype / drug effects
  • Influenza A virus / drug effects*
  • Influenza B virus / drug effects
  • Influenza, Human / drug therapy
  • Influenza, Human / virology
  • MAP Kinase Signaling System / drug effects
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / administration & dosage
  • Oligopeptides / antagonists & inhibitors*
  • Oseltamivir / pharmacology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors*
  • Receptors, Formyl Peptide / antagonists & inhibitors*
  • Receptors, Lipoxin / antagonists & inhibitors*
  • Sequence Alignment
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Drug Combinations
  • FPR2 protein, human
  • Gelsolin
  • Oligopeptides
  • Peptide Fragments
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • gelsolin (160-169)
  • Oseltamivir
  • butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine