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First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery
ABSTRACT: Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the str...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782049/ https://www.ncbi.nlm.nih.gov/pubmed/33400085 http://dx.doi.org/10.1007/s11030-020-10166-3 |
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author | Amin, Sk. Abdul Banerjee, Suvankar Singh, Samayaditya Qureshi, Insaf Ahmed Gayen, Shovanlal Jha, Tarun |
author_facet | Amin, Sk. Abdul Banerjee, Suvankar Singh, Samayaditya Qureshi, Insaf Ahmed Gayen, Shovanlal Jha, Tarun |
author_sort | Amin, Sk. Abdul |
collection | PubMed |
description | ABSTRACT: Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10166-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7782049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-77820492021-01-05 First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery Amin, Sk. Abdul Banerjee, Suvankar Singh, Samayaditya Qureshi, Insaf Ahmed Gayen, Shovanlal Jha, Tarun Mol Divers Original Article ABSTRACT: Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10166-3) contains supplementary material, which is available to authorized users. Springer International Publishing 2021-01-05 2021 /pmc/articles/PMC7782049/ /pubmed/33400085 http://dx.doi.org/10.1007/s11030-020-10166-3 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Article Amin, Sk. Abdul Banerjee, Suvankar Singh, Samayaditya Qureshi, Insaf Ahmed Gayen, Shovanlal Jha, Tarun First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title_full | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title_fullStr | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title_full_unstemmed | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title_short | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
title_sort | first structure–activity relationship analysis of sars-cov-2 virus main protease (mpro) inhibitors: an endeavor on covid-19 drug discovery |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782049/ https://www.ncbi.nlm.nih.gov/pubmed/33400085 http://dx.doi.org/10.1007/s11030-020-10166-3 |
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