Research output: Contribution to journal › Article › peer-review
Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3'-Termini. / Yuyukina, S K; Barmatov, A E; Bizyaev, S N et al.
In: Doklady. Biochemistry and biophysics, Vol. 509, No. 1, 04.2023, p. 65-69.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3'-Termini
AU - Yuyukina, S K
AU - Barmatov, A E
AU - Bizyaev, S N
AU - Stetsenko, D A
AU - Sergeeva, O V
AU - Zatsepin, T S
AU - Zharkov, D O
N1 - Funding: This study was supported by the Russian Foundation for Basic Research (project no. 20-04-60433) and the Ministry of Science and Higher Education of the Russian Federation (project of Novosibirsk State University no. FSUS-2020-0035). © 2023. Pleiades Publishing, Ltd.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Humans
KW - SARS-CoV-2/genetics
KW - COVID-19
KW - Exonucleases
KW - Pandemics
KW - RNA, Viral/genetics
KW - Nucleotides
KW - Antiviral Agents/pharmacology
KW - Virus Replication/genetics
KW - RNA oligonucleotides
KW - antiviral drugs
KW - coronaviruses
KW - nsp14
KW - nsp10
KW - nucleoside inhibitors
KW - replication proofreading
KW - exonucleases
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85162928320&origin=inward&txGid=e98eb6ba9e2a6745c1b0559cda11eca6
UR - https://www.mendeley.com/catalogue/c5023112-14db-3009-b341-c170f5a07492/
U2 - 10.1134/S1607672923700102
DO - 10.1134/S1607672923700102
M3 - Article
C2 - 37340295
VL - 509
SP - 65
EP - 69
JO - Doklady Biochemistry and Biophysics
JF - Doklady Biochemistry and Biophysics
SN - 1607-6729
IS - 1
ER -
ID: 53440720