Open AccessStructure–function analysis of the nsp14 N7–guanine methyltransferase reveals an essential role inBetacoronavirusreplication
Author(s) -
Natacha S. Ogando,
Priscila El Kazzi,
Jessika C. Zevenhoven-Dobbe,
Brenda Wilhelmina Bontes,
Alice Decombe,
Clara C. Posthuma,
Volker Thiel,
Bruno Canard,
François Ferrón,
Étienne Decroly,
Eric J. Snijder
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108709118
Subject(s) - biology , coronavirus , nidovirales , mutation , viral replication , genetics , mutagenesis , betacoronavirus , exon , in silico , viral protein , virus , gene , covid-19 , medicine , disease , pathology , infectious disease (medical specialty)
Significance The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emphasizes the urgent need to develop efficient broad-spectrum anti-CoV drugs. The structure–function characterization of conserved CoV replicative enzymes is key to identifying the most suitable drug targets. Using a multidisciplinary comparative approach and different betacoronaviruses, we characterized the key conserved residues of the nsp14 (N7-guanine)–methyltransferase, a poorly defined subunit of the CoV messenger RNA–synthesizing machinery. Our study highlights the unique structural features of this enzyme and establishes its essential role in betacoronavirus replication, while identifying two residues that are critical for the replication of the four betacoronaviruses tested, including SARS-CoV-2.