The adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus

Chem Biol. 2005 Mar;12(3):303-11. doi: 10.1016/j.chembiol.2005.01.006.

Abstract

Bananins are a class of antiviral compounds with a unique structural signature incorporating a trioxa-adamantane moiety covalently bound to a pyridoxal derivative. Six members of this class of compounds: bananin, iodobananin, vanillinbananin, ansabananin, eubananin, and adeninobananin were synthesized and tested as inhibitors of the SARS Coronavirus (SCV) helicase. Bananin, iodobananin, vanillinbananin, and eubananin were effective inhibitors of the ATPase activity of the SCV helicase with IC50 values in the range 0.5-3 microM. A similar trend, though at slightly higher inhibitor concentrations, was observed for inhibition of the helicase activities, using a FRET-based fluorescent assay. In a cell culture system of SCV, bananin exhibited an EC50 of less than 10 microM and a CC50 of over 300 microM. Kinetics of inhibition are consistent with bananin inhibiting an intracellular process or processes involved in SCV replication.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Adamantane / pharmacology*
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • DNA Helicases / antagonists & inhibitors*
  • DNA Helicases / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Macaca mulatta
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • SARS Virus / drug effects*
  • SARS Virus / enzymology*
  • SARS Virus / physiology
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Pyridines
  • bananin
  • DNA Helicases
  • Adamantane