Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies

Introduction: The recent outbreak of SARS-CoV-2 has significantly increased the need to find inhibitors that target the essential enzymes for viral replication in host cells. This systematic review was conducted to identify potential inhibitors of SARS-CoV, MERS-CoV, and SARS-CoV-2 helicases that ha...

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Main Author: Nimer Mehyar
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Journal of Virus Eradication
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2055664023000134
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author Nimer Mehyar
author_facet Nimer Mehyar
author_sort Nimer Mehyar
collection DOAJ
description Introduction: The recent outbreak of SARS-CoV-2 has significantly increased the need to find inhibitors that target the essential enzymes for viral replication in host cells. This systematic review was conducted to identify potential inhibitors of SARS-CoV, MERS-CoV, and SARS-CoV-2 helicases that have been tested by in vitro methods. Their inhibitory mechanisms are discussed in this review, in addition to their cytotoxic and protective properties. Methods: The databases PUBMED/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched using different combinations of the keywords “helicase”, “nsp13”, “inhibitors”, “coronaviridae”, “coronaviruses”, “virus replication”, “replication”, and “antagonists and inhibitors''. Results: A total of 6854 articles were identified. Thirty-one were included into this review. These studies reported on the inhibitory effects of 309 compounds on SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase activities measured by in vitro methods. Helicase inhibitors were categorized according to the type of coronavirus and tested enzymatic activity, nature, approval, inhibition level, cytotoxicity, and viral infection protective effects. These inhibitors are classified according to the site of their interaction with coronavirus helicases into four types: zinc-binding site inhibitors, nucleic acid-binding site inhibitors, nucleotide-binding site inhibitors, and inhibitors with no clear interaction site. Conclusion: Evidence from in vitro studies suggests that helicase inhibitors have a high potential as antiviral agents. Several show good antiviral activity while maintaining moderate cytotoxicity. These inhibitors should be clinically investigated to determine their efficacy in treating coronavirus infections, particularly SARS-CoV-2.
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spelling doaj.art-ee2d1230ec4a4a1c9f94e3abdb7233432023-07-02T04:16:29ZengElsevierJournal of Virus Eradication2055-66402023-06-0192100327Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studiesNimer Mehyar0King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.Introduction: The recent outbreak of SARS-CoV-2 has significantly increased the need to find inhibitors that target the essential enzymes for viral replication in host cells. This systematic review was conducted to identify potential inhibitors of SARS-CoV, MERS-CoV, and SARS-CoV-2 helicases that have been tested by in vitro methods. Their inhibitory mechanisms are discussed in this review, in addition to their cytotoxic and protective properties. Methods: The databases PUBMED/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched using different combinations of the keywords “helicase”, “nsp13”, “inhibitors”, “coronaviridae”, “coronaviruses”, “virus replication”, “replication”, and “antagonists and inhibitors''. Results: A total of 6854 articles were identified. Thirty-one were included into this review. These studies reported on the inhibitory effects of 309 compounds on SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase activities measured by in vitro methods. Helicase inhibitors were categorized according to the type of coronavirus and tested enzymatic activity, nature, approval, inhibition level, cytotoxicity, and viral infection protective effects. These inhibitors are classified according to the site of their interaction with coronavirus helicases into four types: zinc-binding site inhibitors, nucleic acid-binding site inhibitors, nucleotide-binding site inhibitors, and inhibitors with no clear interaction site. Conclusion: Evidence from in vitro studies suggests that helicase inhibitors have a high potential as antiviral agents. Several show good antiviral activity while maintaining moderate cytotoxicity. These inhibitors should be clinically investigated to determine their efficacy in treating coronavirus infections, particularly SARS-CoV-2.http://www.sciencedirect.com/science/article/pii/S2055664023000134CoronavirusHelicaseInhibitorsnsp13In vitro assaySystematic review
spellingShingle Nimer Mehyar
Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
Journal of Virus Eradication
Coronavirus
Helicase
Inhibitors
nsp13
In vitro assay
Systematic review
title Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
title_full Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
title_fullStr Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
title_full_unstemmed Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
title_short Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies
title_sort coronaviruses sars cov mers cov and sars cov 2 helicase inhibitors a systematic review of in vitro studies
topic Coronavirus
Helicase
Inhibitors
nsp13
In vitro assay
Systematic review
url http://www.sciencedirect.com/science/article/pii/S2055664023000134
work_keys_str_mv AT nimermehyar coronavirusessarscovmerscovandsarscov2helicaseinhibitorsasystematicreviewofinvitrostudies