Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms

Molecules. 2020 Sep 7;25(18):4082. doi: 10.3390/molecules25184082.

Abstract

Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain-Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies.

Keywords: Zika virus; antiviral; binding; entry; harringtonine; replication.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Harringtonines / chemistry
  • Harringtonines / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • Vero Cells
  • Viral Envelope Proteins / antagonists & inhibitors
  • Viral Envelope Proteins / chemistry
  • Virus Attachment / drug effects
  • Virus Internalization / drug effects
  • Virus Release
  • Virus Replication / drug effects
  • Zika Virus / drug effects*
  • Zika Virus / genetics
  • Zika Virus Infection / drug therapy
  • Zika Virus Infection / virology*

Substances

  • Antiviral Agents
  • Harringtonines
  • Viral Envelope Proteins