Pinanamine Is a Promising Lead Compound against Influenza A Virus: Evidence from in Vitro and in Vivo Efficacy Compared to Amantadine

Biol Pharm Bull. 2017;40(7):954-959. doi: 10.1248/bpb.b16-00774.

Abstract

Influenza A viruses with the presence of mutations in M2 still circulate and threaten to avian species and human in China. A novel M2 inhibitor pinanamine was previously identified as an antiviral agent by an in vitro assay. In this study, we monitored the activity of pinanamine against influenza A/FM1/47 (H1N1) virus infection in cell culture and mice. Pinanamine showed more potent antiviral effect than ribavirin, and was as effective as oseltamivir carboxylate and amantadine in Madin-Darby canine kidney (MDCK) cells. Pinanamine at dose of 50 mg/kg/d administrated once a day for 6 d starting 24 h prior to virus exposure promoted survival rate of infected mice to 100% (p<0.001) and produced significant reduction (p<0.001) in lung virus yields and lung index. Even lower the dose of 3.1 mg/kg/d, pinanamine was 60% protective (p<0.05), which was equivalent to treatment with amantadine at 50 mg/kg/d. Our finding highlights the potential of pinanamine as a promising lead compound for influenza A virus.

Keywords: M2 inhibitor; in vitro; in vivo; influenza A virus; pinanamine.

MeSH terms

  • Amantadine / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • Dogs
  • Female
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antiviral Agents
  • Imidazoles
  • pinanamine
  • Amantadine