Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA.
Proc Natl Acad Sci U S A
; 115(2): E162-E171, 2018 01 09.
Article
em En
| MEDLINE
| ID: mdl-29279395
ABSTRACT
Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (â¼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3'-5' exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3'-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5'-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribavirina
/
Replicação Viral
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RNA Viral
/
Coronavirus
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França