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One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

Identifieur interne : 001607 ( Main/Exploration ); précédent : 001606; suivant : 001608

One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

Auteurs : Lorenzo Subissi [France] ; Clara C. Posthuma [Pays-Bas] ; Axelle Collet [France] ; Jessika C. Zevenhoven-Dobbe [Pays-Bas] ; Alexander E. Gorbalenya [Pays-Bas, Russie] ; Etienne Decroly [France] ; Eric J. Snijder [Pays-Bas] ; Bruno Canard [France] ; Isabelle Imbert [France]

Source :

RBID : PMC:4169972

Descripteurs français

English descriptors

Abstract

Significance

The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.


Url:
DOI: 10.1073/pnas.1323705111
PubMed: 25197083
PubMed Central: 4169972


Affiliations:


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


Le document en format XML

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<title>Significance</title>
<p>The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.</p>
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