Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3'-Termini.
RNA oligonucleotides
antiviral drugs
coronaviruses
exonucleases
nsp10
nsp14
nucleoside inhibitors
replication proofreading
Journal
Doklady. Biochemistry and biophysics
ISSN: 1608-3091
Titre abrégé: Dokl Biochem Biophys
Pays: United States
ID NLM: 101126895
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
25
11
2022
accepted:
09
12
2022
revised:
05
12
2022
medline:
22
6
2023
pubmed:
21
6
2023
entrez:
20
6
2023
Statut:
ppublish
Résumé
The COVID-19 pandemic has shown the urgent need for new treatments for coronavirus infections. Nucleoside analogs were successfully used to inhibit replication of some viruses through the incorporation into the growing DNA or RNA chain. However, the replicative machinery of coronaviruses contains nsp14, a non-structural protein with a 3'→5'-exonuclease activity that removes misincorporated and modified nucleotides from the 3' end of the growing RNA chain. Here, we studied the efficiency of hydrolysis of RNA containing various modifications in the 3'-terminal region by SARS-CoV-2 nsp14 exonuclease and its complex with the auxiliary protein nsp10. Single-stranded RNA was a preferable substrate compared to double-stranded RNA, which is consistent with the model of transfer of the substrate strand to the exonuclease active site, which was proposed on the basis of structural analysis. Modifications of the phosphodiester bond between the penultimate and last nucleotides had the greatest effect on nsp14 activity.
Identifiants
pubmed: 37340295
doi: 10.1134/S1607672923700102
pii: 10.1134/S1607672923700102
doi:
Substances chimiques
Exonucleases
EC 3.1.-
RNA, Viral
0
Nucleotides
0
Antiviral Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-69Informations de copyright
© 2023. Pleiades Publishing, Ltd.
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