Serveur d'exploration SRAS

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

Identifieur interne : 002487 ( Main/Exploration ); précédent : 002486; suivant : 002488

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

Auteurs : 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

Source :

RBID : PMC:7164005

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.


Url:
DOI: 10.1111/j.1742-4658.2010.07961.x
PubMed: 21134131
PubMed Central: 7164005


Affiliations:


Links toward previous steps (curation, corpus...)


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<p>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.</p>
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