Abstract: Moreover, infection with rSARS-CoV-2nsp14-Y420A conferred complete protection against subsequent and otherwise lethal SARS-CoV-2 infection in mice, indicating the vaccine potential of this mutant.
Abstract: We further found that the comparable mutation (Y420A) in SARS-CoV-2 nsp14 (rSARS-CoV-2nsp14-Y420A) also significantly decreased N7-methyltransferase activity in vitro, and the mutant virus was attenuated in K18-human ACE2 transgenic mice.
Live attenuated coronavirus vaccines deficient in N7-Methyltransferase activity induce both humoral and cellular immune responses in mice.
Result: Further structure-function analysis suggested that the single amino acid substitution D331A, which is in the DxG S-adenosyl-L-methionine (SAM)-binding motif, and Y420A, which is in the supporting structure of the SAM-binding pocket, can affect the SAM-binding affinity of SARS-CoV N7-MTase and abolish its N7-methylation activity in vitro.
Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role in Betacoronavirus replication.
Result: Four of the five mutations (Y420A and H424A in SARS-CoV, and W292A and H420A in MERS-CoV) that affected ExoN activity mapped to the hinge region.
Result: In contrast, the ExoN activity of SARS-CoV mutants R310A, Y420A, and H424A and MERS-CoV mutant W292A was strongly or partially affected, as indicated by the reduced amount of hydrolysis products at the bottom of the gel.
Result: Thus, our data confirmed and extended a previous study and showed that N7-MTase activity is affected by mutations that either may inhibit SAM binding (W292A, D331A,
SARS_CoV_2 mutation literature information.
PMID: 
2022
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