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.
© 2010 The Authors Journal compilation © 2010 FEBS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adamantane / analogs & derivatives*
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Adamantane / chemistry
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Adamantane / metabolism
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Adamantane / pharmacology
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Adamantane / therapeutic use
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Binding Sites / genetics
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Computational Biology
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Coronavirus M Proteins
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DNA Helicases / chemistry
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DNA Helicases / genetics
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DNA Helicases / metabolism
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Drug Resistance, Viral / genetics*
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Membrane Glycoproteins / genetics
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Models, Molecular
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Mutation, Missense / genetics
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Protein Binding / genetics
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Protein Structure, Quaternary
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Pyridines / chemistry
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Pyridines / metabolism
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Pyridines / pharmacology*
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Pyridines / therapeutic use
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RNA Helicases / chemistry
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RNA Helicases / genetics
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RNA Helicases / metabolism
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Severe Acute Respiratory Syndrome / drug therapy
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Severe acute respiratory syndrome-related coronavirus / genetics*
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Spike Glycoprotein, Coronavirus
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Static Electricity
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Viral Envelope Proteins / genetics
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Viral Matrix Proteins / genetics
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Viral Proteins / chemistry
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Viral Proteins / genetics*
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Viral Proteins / metabolism
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Water / chemistry
Substances
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Coronavirus M Proteins
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M protein, SARS-CoV
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Membrane Glycoproteins
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Pyridines
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Spike Glycoprotein, Coronavirus
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Viral Envelope Proteins
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Viral Matrix Proteins
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Viral Proteins
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bananin
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Water
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DNA Helicases
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RNA Helicases
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Adamantane