Recent Advances Towards Drug Design Targeting the Protease of 2019 Novel Coronavirus (2019-nCoV).

ATP SARSCoV- 2 coronavirus non-structural proteins protease-like 3-chymotrypsin (3CLpro) protease-like papain (PLpro) remdesivir

Journal

Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157

Informations de publication

Date de publication:
2021
Historique:
received: 24 07 2020
revised: 16 09 2020
accepted: 24 09 2020
pubmed: 29 10 2020
medline: 17 8 2021
entrez: 28 10 2020
Statut: ppublish

Résumé

The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes time, there is a possibility offindingan effective treatment from existing antiviral agents. The aim of this study is to find out the relationship between thepossible drug targets and themechanism of action of antiviral drugs. This review discusses the efforts indevelopingdrug from known or new molecules. Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of thecoronavirus. Certain antiviral drugs such as Remdesivir are RNA-dependent RNA polymerase inhibitorswiththe ability to terminate RNA replication by inhibiting ATP. It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents havebeen discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus. In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.

Sections du résumé

BACKGROUND BACKGROUND
The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes time, there is a possibility offindingan effective treatment from existing antiviral agents.
OBJECTIVE OBJECTIVE
The aim of this study is to find out the relationship between thepossible drug targets and themechanism of action of antiviral drugs. This review discusses the efforts indevelopingdrug from known or new molecules.
METHODS METHODS
Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of thecoronavirus. Certain antiviral drugs such as Remdesivir are RNA-dependent RNA polymerase inhibitorswiththe ability to terminate RNA replication by inhibiting ATP.
RESULTS RESULTS
It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents havebeen discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus.
CONCLUSION CONCLUSIONS
In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.

Identifiants

pubmed: 33109027
pii: CMC-EPUB-110962
doi: 10.2174/0929867327666201027153617
doi:

Substances chimiques

Antiviral Agents 0
Peptide Hydrolases EC 3.4.-

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

4484-4498

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Sehrish Bano (S)

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

Abdul Hameed (A)

Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan.

Mariya Al-Rashida (M)

Department of Chemistry, Forman Christian College (A Chartered University), Lahore, Pakistan.

Shafia Iftikhar (S)

Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan.

Jamshed Iqbal (J)

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

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Classifications MeSH