TY - JOUR

T1 - Mechanisms of Coronavirus Genome Stability As Potential Targets for Antiviral Drugs

AU - Yuyukina, S. K.

AU - Zharkov, D. O.

N1 - Funding Information: This study was supported by the Russian Foundation for Basic Research, project no. 20-04-60433. Publisher Copyright: © 2022, Pleiades Publishing, Ltd.

PY - 2022/8

Y1 - 2022/8

N2 - The COVID-19 pandemic has made it necessary to create antivirals active against the SARS-CoV-2 coronavirus. One of the widely used strategies to fight off viral infections is the use of modified nucleoside analogues that inhibit viral replication by incorporating DNA or RNA into the growing chain, thus stopping its synthesis. The difficulty of using this method of treatment in the case of SARS-CoV-2 is that coronaviruses have an effective mechanism for maintaining genome stability. Its central element is the nsp14 protein, which is characterized by exonuclease activity, due to which incorrectly included and noncanonical nucleotides are removed from the 3' end of the growing RNA chain. Inhibitors of nsp14 exonuclease and nucleoside analogues resistant to its action are viewed as potential targets for anticoronavirus therapy.

AB - The COVID-19 pandemic has made it necessary to create antivirals active against the SARS-CoV-2 coronavirus. One of the widely used strategies to fight off viral infections is the use of modified nucleoside analogues that inhibit viral replication by incorporating DNA or RNA into the growing chain, thus stopping its synthesis. The difficulty of using this method of treatment in the case of SARS-CoV-2 is that coronaviruses have an effective mechanism for maintaining genome stability. Its central element is the nsp14 protein, which is characterized by exonuclease activity, due to which incorrectly included and noncanonical nucleotides are removed from the 3' end of the growing RNA chain. Inhibitors of nsp14 exonuclease and nucleoside analogues resistant to its action are viewed as potential targets for anticoronavirus therapy.

KW - corrective exonuclease

KW - COVID-19

KW - genome stability

KW - nucleoside inhibitors

KW - replication

KW - RNA-dependent RNA polymerase

KW - SARS-CoV-2

UR - http://www.scopus.com/inward/record.url?scp=85138033857&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/fe163be1-088b-33ac-affe-393d5451ecc4/

U2 - 10.1134/S1019331622040256

DO - 10.1134/S1019331622040256

M3 - Article

C2 - 36091852

AN - SCOPUS:85138033857

VL - 92

SP - 470

EP - 478

JO - Herald of the Russian Academy of Sciences

JF - Herald of the Russian Academy of Sciences

SN - 1019-3316

IS - 4

ER -