Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions

J Med Virol. 2012 Jan;84(1):170-81. doi: 10.1002/jmv.22234. Epub 2011 Oct 25.

Abstract

The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8 µg/ml (0.41-22 nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6 µg/ml); greater inhibition occurred when end-points were expressed as TCID(50) s. For respiratory syncytial virus (RSV), a reduction in plaque size but not number was observed. However, when the drug was added to infected cultures (≥5 µg/ml), a 3-log reduction in titer occurred. Arbidol did not inhibit directly influenza A/Aichi/2/68 hemagglutinin (HA) or neuraminidase (NA) activity, but inhibition of fusion between the viral envelope and chicken red blood cells occurred when added at 0.1 µg/ml prior to infection. Arbidol induced changes to viral mRNA synthesis of the PB2, PA, NP, NA, and NS genes in MDCK cultures infected with influenza A/PR/8/34. There was no indirect evidence of enhancement of interferon-α by arbidol following infection with A/Aichi/2/68. Arbidol neither reduced lung viral titers nor caused a significant reduction of lung consolidation in BALB/c mice after administration by the oral and intraperitoneal (i.p.) routes and intranasal challenge with influenza A/Aichi/2/68. A small reduction in lung consolidation, but not viral titer, occurred after i.p. administration and subsequent challenge with RSV. The results indicate the potential of arbidol as a broad-spectrum respiratory antiviral drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Lung / pathology
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests / methods
  • Orthomyxoviridae Infections / drug therapy
  • Respiratory Tract Infections / virology*
  • Viral Load
  • Viral Plaque Assay
  • Viruses / drug effects*
  • Viruses / isolation & purification

Substances

  • Antiviral Agents
  • Indoles
  • umifenovir