Inhibitory effect of 2,4-dichlorophenoxyacetic acid on ROS, autophagy formation, and mRNA replication for influenza virus infection

J Mol Recognit. 2017 Aug;30(8). doi: 10.1002/jmr.2616. Epub 2017 Feb 24.

Abstract

Influenza virus has had a high rate of antigenic shift and drift that causes significant morbidity and mortality in humans and animals. The lack of excellent pharmacological treatment underlines the importance of the development of the novel antiviral drugs. We investigated the anti-influenza A and B viruses of 2,4-dichlorophenoxyacetic acid (2,4-D), which is the synthetic analog to auxin and is used as a popular herbicide in the agricultural practices. 2,4-D was evaluated using a cytopathic effect reduction method; assay results showed that 2,4-D possessed strong anti-influenza A and B viruses inhibiting the formation of a visible cytopathic effect. Influenza viral RNA expression was performed by quantitative real-time polymerase chain reaction. 2,4-D also inhibited virus replication in the early stage of influenza virus infection without direct interaction with virus particles. Additionally, 2,4-D significantly inhibited various factors occur during influenza virus infection as the acidic vesicular formation and reactive oxygen species production. Moreover, 2,4-D represented no cytotoxicity in normal kidney cell. Therefore, these findings provide an understanding of the mechanism and efficient use of 2,4-D in pharmacological applications against influenza virus infection.

Keywords: 2,4-Dichlorophenoxyacetic acid; ROS; autophagy; influenza virus; viral PB2 subunit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,4-Dichlorophenoxyacetic Acid / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • Autophagy / drug effects*
  • Dogs
  • Gene Expression Regulation, Viral*
  • Host-Pathogen Interactions
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / metabolism
  • Madin Darby Canine Kidney Cells
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / genetics
  • Neuraminidase / metabolism
  • Oseltamivir / pharmacology
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • PB2 protein, influenza virus
  • RNA, Messenger
  • RNA, Viral
  • Reactive Oxygen Species
  • Viral Proteins
  • Oseltamivir
  • 2,4-Dichlorophenoxyacetic Acid
  • Neuraminidase