tetano
Editor, Senior Moderator
J Med Virol
. 2021 Apr 10.
doi: 10.1002/jmv.27009. Online ahead of print.
Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target
Mohammed Tahir[SUP] 1 [/SUP]
Affiliations
Abstract
The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) possesses a non-structural protein (nsp14), with amino terminal domain coding for a proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genome replication and transcription to proofread and exclude mismatched nucleotides has long hindered the development of anti-CoV drugs. The resistance of SARS-CoV-2 to antivirals, especially nucleoside analogs (NAs), shows the need to identify new CoV inhibition targets. Therefore, this review highlights the importance of nsp14-ExoN as a target for inhibition. Also, nucleoside analogs could be used in combination with existing anti-CoV therapeutics to target the proofreading mechanism. This article is protected by copyright. All rights reserved.
Keywords: Coronavirus; Exoribonuclease; Proofreading; RNA recombination; non-structural protein 14.
. 2021 Apr 10.
doi: 10.1002/jmv.27009. Online ahead of print.
Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target
Mohammed Tahir[SUP] 1 [/SUP]
Affiliations
- PMID: 33837972
- DOI: 10.1002/jmv.27009
Abstract
The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) possesses a non-structural protein (nsp14), with amino terminal domain coding for a proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genome replication and transcription to proofread and exclude mismatched nucleotides has long hindered the development of anti-CoV drugs. The resistance of SARS-CoV-2 to antivirals, especially nucleoside analogs (NAs), shows the need to identify new CoV inhibition targets. Therefore, this review highlights the importance of nsp14-ExoN as a target for inhibition. Also, nucleoside analogs could be used in combination with existing anti-CoV therapeutics to target the proofreading mechanism. This article is protected by copyright. All rights reserved.
Keywords: Coronavirus; Exoribonuclease; Proofreading; RNA recombination; non-structural protein 14.