Screening and pharmacodynamic evaluation of the anti-respiratory syncytial virus activity of butene lactones in vitro and in vivo

J Med Virol. 2020 Jan;92(1):17-25. doi: 10.1002/jmv.25586. Epub 2019 Sep 10.

Abstract

A series of butene lactones were synthesized and these compounds were tested for anti-respiratory syncytial virus (RSV) activity in vitro. Three compounds exhibited an antiviral effect, the highest of which was compound 6b3 with an effective concentration 50% of 6.35 μM. The effects of 6b3 were then evaluated in vivo and a significant reduction in the lung index caused by RSV was detected. Reduced inflammatory infiltration and necrosis of the lungs were revealed by histopathology and gross pathology. Activation of an early immune response by 6b3 was also observed by cytokine analysis via a real-time polymerase chain reaction. These results indicated that 6b3 has an anti-RSV effect both in vitro and in vivo, and is a possible candidate compound for the development of an anti-RSV drug in the future.

Keywords: EC50; RSV; butene lactone; molecular mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry
  • Alkenes / pharmacology*
  • Animals
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Drug Discovery
  • High-Throughput Screening Assays
  • Lactones / pharmacokinetics
  • Lactones / pharmacology*
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus, Human / drug effects*
  • Respiratory Syncytial Virus, Human / physiology
  • Specific Pathogen-Free Organisms
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Alkenes
  • Antiviral Agents
  • Lactones
  • butylene