Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx

Life Sci. 2024 Sep 1:352:122877. doi: 10.1016/j.lfs.2024.122877. Epub 2024 Jun 27.

Abstract

Aims: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism.

Materials and methods: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil.

Key findings: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication.

Significance: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

Keywords: Anti-virus; Ca(2+); EGTA; Respiratory syncytial virus; Verapamil.

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium* / metabolism
  • Female
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C*
  • Respiratory Syncytial Virus Infections* / drug therapy
  • Respiratory Syncytial Virus Infections* / metabolism
  • Respiratory Syncytial Virus Infections* / virology
  • Respiratory Syncytial Viruses / drug effects
  • Verapamil* / pharmacology
  • Viral Load / drug effects
  • Virus Replication / drug effects

Substances

  • Verapamil
  • Calcium
  • Antiviral Agents
  • Calcium Channel Blockers