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Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction

The vaccination drive against COVID-19 worldwide was quite successful. However, the second wave of infections was even more disastrous. There was a rapid increase in reinfections and human deaths due to the appearance of new SARS-CoV-2 variants. The viral genome mutations in the variants were acquir...

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Autores principales: Singh, Ruhar, Kumar, Abhijeet, Rane, Jitendra Subhash, Khan, Rajni, Tripathi, Garima, Ajay, Amrendra K., Prakash, Amresh, Ray, Shashikant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552724/
https://www.ncbi.nlm.nih.gov/pubmed/36220880
http://dx.doi.org/10.1038/s41598-022-20759-7
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author Singh, Ruhar
Kumar, Abhijeet
Rane, Jitendra Subhash
Khan, Rajni
Tripathi, Garima
Ajay, Amrendra K.
Prakash, Amresh
Ray, Shashikant
author_facet Singh, Ruhar
Kumar, Abhijeet
Rane, Jitendra Subhash
Khan, Rajni
Tripathi, Garima
Ajay, Amrendra K.
Prakash, Amresh
Ray, Shashikant
author_sort Singh, Ruhar
collection PubMed
description The vaccination drive against COVID-19 worldwide was quite successful. However, the second wave of infections was even more disastrous. There was a rapid increase in reinfections and human deaths due to the appearance of new SARS-CoV-2 variants. The viral genome mutations in the variants were acquired while passing through different human hosts that could escape antibodies in convalescent or vaccinated individuals. The treatment was based on oxygen supplements and supportive protocols due to the lack of a specific drug. In this study, we identified three lead inhibitors of arylated coumarin derivatives 4,6,8-tri(naphthalen-2-yl)-2H-chromen-2-one (NF1), 8-(4-hydroxyphenyl)-4,6-di(naphthalen-2-yl)-2H-chromen-2-one (NF12) and 8-(4-hydroxyphenyl)-3,6-di(naphthalen-2-yl)-2H-chromen-2-one (NF-13) that showed higher binding affinity towards the junction of SARS-CoV-2 spike glycoprotein (S-protein) and human angiotensin-converting enzyme 2 (ACE2) receptor. Using molecular docking analysis, we identified the putative binding sites of these potent inhibitors. Notably, molecular dynamics (MD) simulation and MM-PBSA studies confirmed that these inhibitors have the potential ability to bind Spike-protein/ACE2 protein complex with minimal energy. Further, the two major concerns are an adaptive mutation of spike proteins- N501Y and D614G which displayed strong affinity towards NF-13 in docking analysis. Additionally, in vitro and in vivo studies are required to confirm the above findings and develop the inhibitors as potential drugs against SARS-CoV-2.
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spelling pubmed-95527242022-10-11 Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction Singh, Ruhar Kumar, Abhijeet Rane, Jitendra Subhash Khan, Rajni Tripathi, Garima Ajay, Amrendra K. Prakash, Amresh Ray, Shashikant Sci Rep Article The vaccination drive against COVID-19 worldwide was quite successful. However, the second wave of infections was even more disastrous. There was a rapid increase in reinfections and human deaths due to the appearance of new SARS-CoV-2 variants. The viral genome mutations in the variants were acquired while passing through different human hosts that could escape antibodies in convalescent or vaccinated individuals. The treatment was based on oxygen supplements and supportive protocols due to the lack of a specific drug. In this study, we identified three lead inhibitors of arylated coumarin derivatives 4,6,8-tri(naphthalen-2-yl)-2H-chromen-2-one (NF1), 8-(4-hydroxyphenyl)-4,6-di(naphthalen-2-yl)-2H-chromen-2-one (NF12) and 8-(4-hydroxyphenyl)-3,6-di(naphthalen-2-yl)-2H-chromen-2-one (NF-13) that showed higher binding affinity towards the junction of SARS-CoV-2 spike glycoprotein (S-protein) and human angiotensin-converting enzyme 2 (ACE2) receptor. Using molecular docking analysis, we identified the putative binding sites of these potent inhibitors. Notably, molecular dynamics (MD) simulation and MM-PBSA studies confirmed that these inhibitors have the potential ability to bind Spike-protein/ACE2 protein complex with minimal energy. Further, the two major concerns are an adaptive mutation of spike proteins- N501Y and D614G which displayed strong affinity towards NF-13 in docking analysis. Additionally, in vitro and in vivo studies are required to confirm the above findings and develop the inhibitors as potential drugs against SARS-CoV-2. Nature Publishing Group UK 2022-10-11 /pmc/articles/PMC9552724/ /pubmed/36220880 http://dx.doi.org/10.1038/s41598-022-20759-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Singh, Ruhar
Kumar, Abhijeet
Rane, Jitendra Subhash
Khan, Rajni
Tripathi, Garima
Ajay, Amrendra K.
Prakash, Amresh
Ray, Shashikant
Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title_full Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title_fullStr Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title_full_unstemmed Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title_short Arylcoumarin perturbs SARS-CoV-2 pathogenesis by targeting the S-protein/ACE2 interaction
title_sort arylcoumarin perturbs sars-cov-2 pathogenesis by targeting the s-protein/ace2 interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552724/
https://www.ncbi.nlm.nih.gov/pubmed/36220880
http://dx.doi.org/10.1038/s41598-022-20759-7
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