T-type calcium channels blockers inhibit HSV-2 infection at the late stage of genome replication

Eur J Pharmacol. 2021 Feb 5:892:173782. doi: 10.1016/j.ejphar.2020.173782. Epub 2020 Dec 3.

Abstract

Herpes simplex virus type 2 (HSV-2) is a highly contagious sexually transmitted virus. The increasing emergence of drug-resistant viral strains has highlighted the crucial need for the development of new anti-HSV-2 drugs with different mechanisms. Ion channels that govern a wide range of cellular functions represent attractive targets for viral manipulation. Here, we tried to identify novel compounds to suppress HSV-2 infection in vitro by screening a small library with ion channels modulators. We found that several T-type calcium channel blockers including benidipine, lercanidipine, lomerizine and mibefradil inhibited HSV-2 infection, while L-type calcium channel blockers nifedipine and nitrendipine showed no significant effect on HSV-2 infection. Furthermore, we found that benidipine exerted the antiviral effect by suppressing the expression of viral genes in the late stage of viral infection. In conclusion, our study suggested that T-type calcium channel blockers, which are clinically wide used, could effectively inhibit HSV-2 infection. These findings could shed light on the mechanism and pharmacological study for HSV-2 infection in the future.

Keywords: Benidipine; Calcium channel blockers; HSV-2; Voltage-gated calcium channel.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Calcium Channels, T-Type / metabolism
  • Calcium Signaling / drug effects*
  • Chlorocebus aethiops
  • Dihydropyridines / pharmacology
  • Gene Expression Regulation, Viral / drug effects
  • HeLa Cells
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / metabolism
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / growth & development
  • Host-Pathogen Interactions
  • Humans
  • Piperazines / pharmacology
  • Vero Cells
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Dihydropyridines
  • Piperazines
  • benidipine
  • lomerizine
  • lercanidipine