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

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.

• Authors: Zai Wang, Jian-Dong Huang, Kin-Ling Wong, Pei-Gang Wang, Hao-Jie Zhang, Julian A Tanner, Ottavia Spiga, Andrea Bernini, Bo-Jian Zheng, Neri Niccolai
• Journal: The FEBS journal (FEBS J) Vol. 278 Issue 2 Pg. 383-9 (Jan 2011) ISSN: 1742-4658 [Electronic] England
• PMID: 21134131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors Journal compilation © 2010 FEBS.

Chemical References

• 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

Topics

• Adamantane (analogs & derivatives, chemistry, metabolism, pharmacology, therapeutic use)
• Binding Sites (genetics)
• Computational Biology
• Coronavirus M Proteins
• DNA Helicases (chemistry, genetics, 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, metabolism, pharmacology, therapeutic use)
• RNA Helicases (chemistry, genetics, metabolism)
• Severe acute respiratory syndrome-related coronavirus (drug effects, genetics)
• Severe Acute Respiratory Syndrome (drug therapy)
• Spike Glycoprotein, Coronavirus
• Static Electricity
• Viral Envelope Proteins (genetics)
• Viral Matrix Proteins (genetics)
• Viral Proteins (chemistry, genetics, metabolism)
• Water (chemistry)