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Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease
No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527826/ https://www.ncbi.nlm.nih.gov/pubmed/33011363 http://dx.doi.org/10.1016/j.micpath.2020.104546 |
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author | Basu, Soumya Veeraraghavan, Balaji Ramaiah, Sudha Anbarasu, Anand |
author_facet | Basu, Soumya Veeraraghavan, Balaji Ramaiah, Sudha Anbarasu, Anand |
author_sort | Basu, Soumya |
collection | PubMed |
description | No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with binding energy (−8.72 kcal/mol) better than that of popularly devised anti-Covid-19 drugs like viral protease inhibitor Lopinavir, nucleoside analogue Remdesivir and the repurposed drug hydroxychloroquine when targeted to the active-site of SARS-CoV-2 Main protease (Mpro) through docking studies. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41 involving in the protease activity; as well as GLU-166 and ASN-142 which plays the pivotal role in the protein-dimerization. The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies. Based on virtual assessment, ZINC07333416 also have significant values in terms of medicinal chemistry, pharmacokinetics, synthetic accessibility and anti-viral activity that encourage its experimental applications against COVID-19. |
format | Online Article Text |
id | pubmed-7527826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75278262020-10-01 Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease Basu, Soumya Veeraraghavan, Balaji Ramaiah, Sudha Anbarasu, Anand Microb Pathog Article No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with binding energy (−8.72 kcal/mol) better than that of popularly devised anti-Covid-19 drugs like viral protease inhibitor Lopinavir, nucleoside analogue Remdesivir and the repurposed drug hydroxychloroquine when targeted to the active-site of SARS-CoV-2 Main protease (Mpro) through docking studies. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41 involving in the protease activity; as well as GLU-166 and ASN-142 which plays the pivotal role in the protein-dimerization. The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies. Based on virtual assessment, ZINC07333416 also have significant values in terms of medicinal chemistry, pharmacokinetics, synthetic accessibility and anti-viral activity that encourage its experimental applications against COVID-19. Elsevier Ltd. 2020-12 2020-10-01 /pmc/articles/PMC7527826/ /pubmed/33011363 http://dx.doi.org/10.1016/j.micpath.2020.104546 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Basu, Soumya Veeraraghavan, Balaji Ramaiah, Sudha Anbarasu, Anand Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title | Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title_full | Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title_fullStr | Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title_full_unstemmed | Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title_short | Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease |
title_sort | novel cyclohexanone compound as a potential ligand against sars-cov-2 main-protease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527826/ https://www.ncbi.nlm.nih.gov/pubmed/33011363 http://dx.doi.org/10.1016/j.micpath.2020.104546 |
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