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Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates

The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective a...

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Autores principales: Yoshino, Ryunosuke, Yasuo, Nobuaki, Sekijima, Masakazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385649/
https://www.ncbi.nlm.nih.gov/pubmed/32719454
http://dx.doi.org/10.1038/s41598-020-69337-9
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author Yoshino, Ryunosuke
Yasuo, Nobuaki
Sekijima, Masakazu
author_facet Yoshino, Ryunosuke
Yasuo, Nobuaki
Sekijima, Masakazu
author_sort Yoshino, Ryunosuke
collection PubMed
description The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (M(pro)). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 M(pro). However, the mechanism of action of SARS-CoV-2 M(pro) at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 M(pro) and three drug candidates by performing pharmacophore modeling and 1 μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 M(pro).
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spelling pubmed-73856492020-07-29 Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates Yoshino, Ryunosuke Yasuo, Nobuaki Sekijima, Masakazu Sci Rep Article The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (M(pro)). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 M(pro). However, the mechanism of action of SARS-CoV-2 M(pro) at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 M(pro) and three drug candidates by performing pharmacophore modeling and 1 μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 M(pro). Nature Publishing Group UK 2020-07-27 /pmc/articles/PMC7385649/ /pubmed/32719454 http://dx.doi.org/10.1038/s41598-020-69337-9 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yoshino, Ryunosuke
Yasuo, Nobuaki
Sekijima, Masakazu
Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title_full Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title_fullStr Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title_full_unstemmed Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title_short Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates
title_sort identification of key interactions between sars-cov-2 main protease and inhibitor drug candidates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385649/
https://www.ncbi.nlm.nih.gov/pubmed/32719454
http://dx.doi.org/10.1038/s41598-020-69337-9
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