In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening
Infectious agents such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have emerged in recent years causing epidemics with high mortality rates. The quick development of novel therapeutic compounds is required in the fight against such pathogenic agents. Unfortunately, the traditional drug development methods...
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ftdoajarticles:oai:doaj.org/article:9faa0c1223e64684b7c8afad8734225a 2024-09-09T19:28:08+00:00 In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening Harrison Onyango Patrick Odhiambo David Angwenyi Patrick Okoth 2022-01-01T00:00:00Z https://doi.org/10.1155/2022/3697498 https://doaj.org/article/9faa0c1223e64684b7c8afad8734225a EN eng Wiley http://dx.doi.org/10.1155/2022/3697498 https://doaj.org/toc/1687-9694 1687-9694 doi:10.1155/2022/3697498 https://doaj.org/article/9faa0c1223e64684b7c8afad8734225a Journal of Tropical Medicine, Vol 2022 (2022) Arctic medicine. Tropical medicine RC955-962 article 2022 ftdoajarticles https://doi.org/10.1155/2022/3697498 2024-08-05T17:48:37Z Infectious agents such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have emerged in recent years causing epidemics with high mortality rates. The quick development of novel therapeutic compounds is required in the fight against such pathogenic agents. Unfortunately, the traditional drug development methods are time-consuming and expensive. In this study, computational algorithms were utilized for virtual screening of a library of natural compounds in the ZINC database for their affinity towards SARS-CoV-2 Mpro. Compounds such as cinanserin, nelfinavir, baicalin, baicalein, candesartan cilexetil, chloroquine, dipyridamole, and hydroxychloroquine have the ability to prevent SARS-CoV-2 Mpro from facilitating COVID 19 infection; thus, they treat COVID 19. However, these drugs majorly act to reduce the symptoms of the disease. No anti-viral drug against COVID 19 virus infection has been discovered and approved. Therefore, this study sought to explore natural inhibitors of SARS-CoV-2 Mpro to develop a pharmacophore model for virtual screening of natural compounds in the ZINC database as potential candidates for SARS-CoV-2 Mpro inhibitors and as therapeutic molecules against COVID 19. This study undertook in silico methods to identify the best anti-viral candidates targeting SAR-CoV-2 Mpro from natural sources in the ZINC database. Initially, reported anti-SARS-CoV-2 Mpro molecules were integrated into designing a pharmacophore model utilizing PharmaGist. Later, the pharmacophore model was loaded into ZINCPHARMER and screened against the ZINC database to identify new probable drug candidates. The root means square deviation (RMSD) values of the potential drug candidates informed the selection of some of them, which were docked with SARS-CoV-2 Mpro to comprehend their interactions. From the molecular docking results, the top four candidates (ZINC000254823011, ZINC000072307130, ZINC000013627512, and ZINC000009418994) against SARS-CoV-2 Mpro, with binding energies ranging from –8.2 kcal/mol to –8.6 kcal/mol, were examined for ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Journal of Tropical Medicine 2022 1 22 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Harrison Onyango Patrick Odhiambo David Angwenyi Patrick Okoth In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 |
description |
Infectious agents such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have emerged in recent years causing epidemics with high mortality rates. The quick development of novel therapeutic compounds is required in the fight against such pathogenic agents. Unfortunately, the traditional drug development methods are time-consuming and expensive. In this study, computational algorithms were utilized for virtual screening of a library of natural compounds in the ZINC database for their affinity towards SARS-CoV-2 Mpro. Compounds such as cinanserin, nelfinavir, baicalin, baicalein, candesartan cilexetil, chloroquine, dipyridamole, and hydroxychloroquine have the ability to prevent SARS-CoV-2 Mpro from facilitating COVID 19 infection; thus, they treat COVID 19. However, these drugs majorly act to reduce the symptoms of the disease. No anti-viral drug against COVID 19 virus infection has been discovered and approved. Therefore, this study sought to explore natural inhibitors of SARS-CoV-2 Mpro to develop a pharmacophore model for virtual screening of natural compounds in the ZINC database as potential candidates for SARS-CoV-2 Mpro inhibitors and as therapeutic molecules against COVID 19. This study undertook in silico methods to identify the best anti-viral candidates targeting SAR-CoV-2 Mpro from natural sources in the ZINC database. Initially, reported anti-SARS-CoV-2 Mpro molecules were integrated into designing a pharmacophore model utilizing PharmaGist. Later, the pharmacophore model was loaded into ZINCPHARMER and screened against the ZINC database to identify new probable drug candidates. The root means square deviation (RMSD) values of the potential drug candidates informed the selection of some of them, which were docked with SARS-CoV-2 Mpro to comprehend their interactions. From the molecular docking results, the top four candidates (ZINC000254823011, ZINC000072307130, ZINC000013627512, and ZINC000009418994) against SARS-CoV-2 Mpro, with binding energies ranging from –8.2 kcal/mol to –8.6 kcal/mol, were examined for ... |
format |
Article in Journal/Newspaper |
author |
Harrison Onyango Patrick Odhiambo David Angwenyi Patrick Okoth |
author_facet |
Harrison Onyango Patrick Odhiambo David Angwenyi Patrick Okoth |
author_sort |
Harrison Onyango |
title |
In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
title_short |
In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
title_full |
In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
title_fullStr |
In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
title_full_unstemmed |
In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening |
title_sort |
in silico identification of new anti-sars-cov-2 main protease (mpro) molecules with pharmacokinetic properties from natural sources using molecular dynamics (md) simulations and hierarchical virtual screening |
publisher |
Wiley |
publishDate |
2022 |
url |
https://doi.org/10.1155/2022/3697498 https://doaj.org/article/9faa0c1223e64684b7c8afad8734225a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Tropical Medicine, Vol 2022 (2022) |
op_relation |
http://dx.doi.org/10.1155/2022/3697498 https://doaj.org/toc/1687-9694 1687-9694 doi:10.1155/2022/3697498 https://doaj.org/article/9faa0c1223e64684b7c8afad8734225a |
op_doi |
https://doi.org/10.1155/2022/3697498 |
container_title |
Journal of Tropical Medicine |
container_volume |
2022 |
container_start_page |
1 |
op_container_end_page |
22 |
_version_ |
1809897414414303232 |