On the mechanisms of bananin activity against severe acute respiratory syndrome coronavirus

FEBS J. 2011 Jan;278(2):383-9. doi: 10.1111/j.1742-4658.2010.07961.x. Epub 2010 Dec 6.

Abstract

In a previous study, severe acute respiratory syndrome coronavirus (SARS-CoV) was cultured in the presence of bananin, an effective adamantane-related molecule with antiviral activity. In the present study, we show that all bananin-resistant variants exhibit mutations in helicase and membrane protein, although no evidence of bananin interference on their mutual interaction has been found. A structural analysis on protein sequence mutations found in SARS-CoV bananin-resistant variants was performed. The S259/L mutation of SARS-CoV helicase is always found in all the identified bananin-resistant variants, suggesting a primary role of this mutation site for bananin activity. From a structural analysis of SARS-CoV predicted helicase structure, S259 is found in a hydrophilic surface pocket, far from the enzyme active sites and outside the helicase dimer interface. The S/L substitution causes a pocket volume reduction that weakens the interaction between bananin and SARS-CoV mutated helicase, suggesting a possible mechanism for bananin antiviral activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Adamantane / metabolism
  • Adamantane / pharmacology
  • Adamantane / therapeutic use
  • Binding Sites / genetics
  • Computational Biology
  • Coronavirus M Proteins
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Drug Resistance, Viral / genetics*
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Membrane Glycoproteins / genetics
  • Models, Molecular
  • Mutation, Missense / genetics
  • Protein Binding / genetics
  • Protein Structure, Quaternary
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use
  • RNA Helicases / chemistry
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • Severe Acute Respiratory Syndrome / drug therapy
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Severe acute respiratory syndrome-related coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus
  • Static Electricity
  • Viral Envelope Proteins / genetics
  • Viral Matrix Proteins / genetics
  • Viral Proteins / chemistry
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism
  • Water / chemistry

Substances

  • Coronavirus M Proteins
  • M protein, SARS-CoV
  • Membrane Glycoproteins
  • Pyridines
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Viral Matrix Proteins
  • Viral Proteins
  • bananin
  • Water
  • DNA Helicases
  • RNA Helicases
  • Adamantane