Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783563830631071744 |
---|---|
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). |
format | Online Article Text |
id | pubmed-7385649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yoshinoryunosuke identificationofkeyinteractionsbetweensarscov2mainproteaseandinhibitordrugcandidates AT yasuonobuaki identificationofkeyinteractionsbetweensarscov2mainproteaseandinhibitordrugcandidates AT sekijimamasakazu identificationofkeyinteractionsbetweensarscov2mainproteaseandinhibitordrugcandidates |