Lipophilic statins inhibit Zika virus production in Vero cells

Sci Rep. 2019 Aug 7;9(1):11461. doi: 10.1038/s41598-019-47956-1.

Abstract

Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family. ZIKV infection has been associated with neurological complications such as microcephaly in newborns and Guillain-Barré syndrome in adults; thus, therapeutic agents are urgently needed. Statins are clinically approved for lowering cholesterol levels to prevent cardiovascular disease but have shown potential as antiviral drugs. In this study, we explored the possibility of utilizing statins as anti-ZIKV drugs. We found that, generally, lipophilic statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, and simvastatin) could reduce ZIKV production in vitro and result in smaller foci of infection. Time-of-drug-addition assay revealed that early treatment with statins is more beneficial than late treatment; however, statins could not completely inhibit the entry stage of ZIKV infection. Furthermore, individual lipophilic statins differed in anti-ZIKV capacity, with fluvastatin being the most efficient at low concentrations. Taken together, this study shows that statins or their derivatives have the potential to be used as anti-ZIKV therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Fluvastatin / chemistry
  • Fluvastatin / pharmacology
  • Fluvastatin / therapeutic use
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Time-to-Treatment
  • Vero Cells
  • Virus Replication / drug effects*
  • Zika Virus / drug effects*
  • Zika Virus / physiology
  • Zika Virus Infection / drug therapy*
  • Zika Virus Infection / virology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Fluvastatin