Antiviral Effects of Menthol on Coxsackievirus B

Viruses. 2020 Mar 28;12(4):373. doi: 10.3390/v12040373.


Coxsackievirus B (CVB) is a common human enterovirus that causes systemic infection but specifically replicates to high titers in the pancreas. It was reported that certain viruses induce mitochondrial fission to support infection. We documented that CVB triggers mitochondrial fission and blocking mitochondrial fission limits infection. The transient receptor potential channels have been implicated in regulating mitochondrial dynamics; namely, the heat and capsaicin receptor transient receptor potential cation channel subfamily V member 1 (TRPV1) contributes to mitochondrial depolarization and fission. When we transiently warmed HeLa cells to 39 °C prior to CVB exposure, infection was heightened, whereas cooling cells to 25 °C reduced infection. Inducing "cold" by stimulating transient receptor potential cation channel subfamily M member 8 (TRPM8) with menthol led to reduced infection and also resulted in lower levels of mitochondrial fission during infection. Additionally, menthol stabilized levels of mitochondrial antiviral signaling (MAVS) which is known to be tied to mitochondrial dynamics. Taken together, this highlights a novel pathway wherein CVB relies on TRPV1 to initiate proviral mitochondrial fission, which may contribute to the disruption of antiviral immunity. TRPM8 has been shown to antagonize TRPV1, and thus we hypothesize that stimulating TRPM8 blocks TRPV1-mediated mitochondrial fragmentation following CVB exposure and attenuates infection.

Keywords: antiviral; coxsackievirus; menthol; mitochondria; pancreas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Coxsackievirus Infections / drug therapy
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / virology
  • Disease Models, Animal
  • Enterovirus B, Human / drug effects*
  • Enterovirus B, Human / physiology*
  • Gene Expression
  • Genes, Reporter
  • Genetic Vectors / genetics
  • HeLa Cells
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Menthol / pharmacology*
  • Mice
  • TRPM Cation Channels / agonists
  • TRPV Cation Channels / antagonists & inhibitors
  • Temperature
  • Virus Replication / drug effects


  • Antiviral Agents
  • TRPM Cation Channels
  • TRPM8 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Menthol