3-Indoleacetonitrile Is Highly Effective in Treating Influenza A Virus Infection In Vitro and In Vivo

Viruses. 2021 Jul 23;13(8):1433. doi: 10.3390/v13081433.

Abstract

Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.

Keywords: 3-indoleacetonitrile; antiviral; indole derivatives; indole-3-carboxaldehyde; influenza A virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Antiviral Agents / toxicity
  • Dogs
  • Female
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use*
  • Indoles / toxicity
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Influenza A Virus, H5N1 Subtype / physiology
  • Influenza A virus / drug effects*
  • Influenza A virus / physiology
  • Lung / pathology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Sulfides / pharmacology
  • Viral Load / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Indoles
  • Sulfides
  • indole-3-carbaldehyde
  • umifenovir
  • indole-3-acetonitrile