6-Hydroxydopamine Inhibits the Hepatitis C Virus through Alkylation of Host and Viral Proteins and the Induction of Oxidative Stress

ACS Infect Dis. 2016 Nov 11;2(11):863-871. doi: 10.1021/acsinfecdis.6b00098. Epub 2016 Oct 13.


Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintricarboxylic acid (ATA), to examine their effects on viral replication. We found that 6-OHDA inhibited HCV replication; however, 6-OHDA was a less potent inhibitor of RISC than either SUR or ATA. By generating a novel chemical probe (6-OHDA-yne), we determined that 6-OHDA covalently modifies host and virus proteins. Moreover, 6-OHDA was shown to be an alkylating agent that is capable of generating adducts with a number of enzymes involved in the oxidative stress response. Furthermore, modification of viral enzymes with 6-OHDA and 6-OHDA-yne was found to inhibit their enzymatic activity. Our findings suggest that 6-OHDA is a probe for oxidative stress as well as protein alkylation, and these properties together contribute to the antiviral effects of this compound.

Keywords: 6-hydroxydopamine; alkylation; antiviral; chemical probe; hepatitis C virus; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Hepatitis C / metabolism*
  • Hepatitis C / virology
  • Humans
  • Oxidative Stress / drug effects*
  • Oxidopamine / pharmacology*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Viral Proteins
  • Oxidopamine