Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease

Coronavirus disease 2019 (COVID-19) has caused more than 840,000 deaths as of 31 August 2020 in the whole world. The COVID-19 main protease (M(pro)) has been validated as an attractive target for drug design. In this work, the binding mechanisms of five protease inhibitors (e.g., danoprevir, darunav...

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Autores principales: Liu, Jian, Zhai, You, Liang, Lijun, Zhu, Danyan, Zhao, Qingwei, Qiu, Yunqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834164/
https://www.ncbi.nlm.nih.gov/pubmed/33519023
http://dx.doi.org/10.1016/j.chemphys.2020.111080
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author Liu, Jian
Zhai, You
Liang, Lijun
Zhu, Danyan
Zhao, Qingwei
Qiu, Yunqing
author_facet Liu, Jian
Zhai, You
Liang, Lijun
Zhu, Danyan
Zhao, Qingwei
Qiu, Yunqing
author_sort Liu, Jian
collection PubMed
description Coronavirus disease 2019 (COVID-19) has caused more than 840,000 deaths as of 31 August 2020 in the whole world. The COVID-19 main protease (M(pro)) has been validated as an attractive target for drug design. In this work, the binding mechanisms of five protease inhibitors (e.g., danoprevir, darunavir, ASC09, lopinavir and ritonavir) to COVID-19 M(pro) were investigated. Based on the docking score, five protease inhibitors structures were selected for further evaluation. It is found that most of the selected drug molecules bind stably to the COVID-19 M(pro) from the molecular dynamics simulation. Moreover, the MM/PBSA free energy calculations suggest that lopinavir with positive charge might be most active against COVID-19 M(pro).
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spelling pubmed-78341642021-01-26 Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease Liu, Jian Zhai, You Liang, Lijun Zhu, Danyan Zhao, Qingwei Qiu, Yunqing Chem Phys Article Coronavirus disease 2019 (COVID-19) has caused more than 840,000 deaths as of 31 August 2020 in the whole world. The COVID-19 main protease (M(pro)) has been validated as an attractive target for drug design. In this work, the binding mechanisms of five protease inhibitors (e.g., danoprevir, darunavir, ASC09, lopinavir and ritonavir) to COVID-19 M(pro) were investigated. Based on the docking score, five protease inhibitors structures were selected for further evaluation. It is found that most of the selected drug molecules bind stably to the COVID-19 M(pro) from the molecular dynamics simulation. Moreover, the MM/PBSA free energy calculations suggest that lopinavir with positive charge might be most active against COVID-19 M(pro). Published by Elsevier B.V. 2021-02-01 2020-12-11 /pmc/articles/PMC7834164/ /pubmed/33519023 http://dx.doi.org/10.1016/j.chemphys.2020.111080 Text en © 2020 Published by Elsevier B.V. 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
Liu, Jian
Zhai, You
Liang, Lijun
Zhu, Danyan
Zhao, Qingwei
Qiu, Yunqing
Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title_full Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title_fullStr Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title_full_unstemmed Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title_short Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease
title_sort molecular modeling evaluation of the binding effect of five protease inhibitors to covid-19 main protease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834164/
https://www.ncbi.nlm.nih.gov/pubmed/33519023
http://dx.doi.org/10.1016/j.chemphys.2020.111080
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