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Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA
Abstract : Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 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.
https://hal-amu.archives-ouvertes.fr/hal-02094607
Contributor : Yves Bourne Connect in order to contact the contributor
Submitted on : Tuesday, April 9, 2019 - 5:30:16 PM
Last modification on : Monday, November 22, 2021 - 2:16:01 PM
Contributor : Yves Bourne Connect in order to contact the contributor
Submitted on : Tuesday, April 9, 2019 - 5:30:16 PM
Last modification on : Monday, November 22, 2021 - 2:16:01 PM
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