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

Identifieur interne : 001460 ( PubMed/Checkpoint ); précédent : 001459; suivant : 001461

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

Auteurs : Zai Wang [République populaire de Chine] ; Jian-Dong Huang ; Kin-Ling Wong ; Pei-Gang Wang ; Hao-Jie Zhang ; Julian A. Tanner ; Ottavia Spiga ; Andrea Bernini ; Bo-Jian Zheng ; Neri Niccolai

Source :

RBID : pubmed:21134131

Descripteurs français

English descriptors

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.

DOI: 10.1111/j.1742-4658.2010.07961.x
PubMed: 21134131


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pubmed:21134131

Le document en format XML

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<div type="abstract" xml:lang="en">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.</div>
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