Antiviral activity of lycorine against Zika virus in vivo and in vitro

Virology. 2020 Jul:546:88-97. doi: 10.1016/j.virol.2020.04.009. Epub 2020 Apr 19.

Abstract

The emergence and re-emergence of Zika virus (ZIKV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas worldwide. Despite these burdens, antiviral therapies do not exist, and inhibitors of ZIKV are therefore urgently needed. To elucidate the anti-ZIKV effect of lycorine, we used reverse transcription-quantitative real-time PCR (qRT-PCR), immunofluorescence, Westernwestern blot, and plaque forming assay to analyse viral RNA (vRNA), viral protein, progeny virus counts, and validated inhibitors in vitro using a variety of cell lines. Additionally, we found that lycorine acts post-infection according to time-of-addition assay, and inhibits RdRp activity. Lycorine protected AG6 mice against ZIKV-induced lethality by decreasing the viral load in the blood. Due to its potency and ability to target ZIKV infection in vivo and in vitro, lycorine might offer promising therapeutic possibilities for combatting ZIKV infections in the future.

Keywords: AG6 mice; Alkaloid; Antiviral; Lycorine; RdRp inhibitor; ZIKV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amaryllidaceae Alkaloids / administration & dosage*
  • Amaryllidaceae Alkaloids / chemistry
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / chemistry
  • Female
  • Humans
  • Male
  • Mice
  • Molecular Docking Simulation
  • Phenanthridines / administration & dosage*
  • Phenanthridines / chemistry
  • Virus Replication / drug effects
  • Zika Virus / drug effects*
  • Zika Virus / genetics
  • Zika Virus / physiology
  • Zika Virus Infection / drug therapy*
  • Zika Virus Infection / mortality
  • Zika Virus Infection / virology

Substances

  • Amaryllidaceae Alkaloids
  • Antiviral Agents
  • Phenanthridines
  • lycorine