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.
Liqiong Ding  1 Ping Jiang  2 Xinfeng Xu  2 Wanzhen Lu  2 Chan Yang  2 Lin Li  3 Pingzheng Zhou  4 Shuwen Liu  5
Affiliations
  • 1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; School of Pharmaceutical Sciences, Hubei University of Science and Technology, Xianning, 437100, China.
  • 2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 3. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, 523808, China. Electronic address: [email protected].
  • 4. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 5. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
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.
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