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Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronaviruses that emerged in China at Wuhan city, Hubei province during December 2019. Subsequently, SARS-CoV-2 has spread worldwide and caused millions of deaths around the globe. Several compounds and vaccines have been propo...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695405/ https://www.ncbi.nlm.nih.gov/pubmed/36432204 http://dx.doi.org/10.3390/molecules27228103 |
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author | Miandad, Khalid Ullah, Asad Bashir, Kashif Khan, Saifullah Abideen, Syed Ainul Shaker, Bilal Alharbi, Metab Alshammari, Abdulrahman Ali, Mahwish Haleem, Abdul Ahmad, Sajjad |
author_facet | Miandad, Khalid Ullah, Asad Bashir, Kashif Khan, Saifullah Abideen, Syed Ainul Shaker, Bilal Alharbi, Metab Alshammari, Abdulrahman Ali, Mahwish Haleem, Abdul Ahmad, Sajjad |
author_sort | Miandad, Khalid |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronaviruses that emerged in China at Wuhan city, Hubei province during December 2019. Subsequently, SARS-CoV-2 has spread worldwide and caused millions of deaths around the globe. Several compounds and vaccines have been proposed to tackle this crisis. Novel recommended in silico approaches have been commonly used to screen for specific SARS-CoV-2 inhibitors of different types. Herein, the phytochemicals of Pakistani medicinal plants (especially Artemisia annua) were virtually screened to identify potential inhibitors of the SARS-CoV-2 main protease enzyme. The X-ray crystal structure of the main protease of SARS-CoV-2 with an N3 inhibitor was obtained from the protein data bank while A. annua phytochemicals were retrieved from different drug databases. The docking technique was carried out to assess the binding efficacy of the retrieved phytochemicals; the docking results revealed that several phytochemicals have potential to inhibit the SARS-CoV-2 main protease enzyme. Among the total docked compounds, the top-10 docked complexes were considered for further study and evaluated for their physiochemical and pharmacokinetic properties. The top-3 docked complexes with the best binding energies were as follows: the top-1 docked complex with a −7 kcal/mol binding energy score, the top-2 docked complex with a −6.9 kcal/mol binding energy score, and the top-3 docked complex with a −6.8 kcal/mol binding energy score. These complexes were subjected to a molecular dynamic simulation analysis for further validation to check the dynamic behavior of the selected top-complexes. During the whole simulation time, no major changes were observed in the docked complexes, which indicated complex stability. Additionally, the free binding energies for the selected docked complexes were also estimated via the MM-GB/PBSA approach, and the results revealed that the total delta energies of MMGBSA were −24.23 kcal/mol, −26.38 kcal/mol, and −25 kcal/mol for top-1, top-2, and top-3, respectively. MMPBSA calculated the delta total energy as −17.23 kcal/mol (top-1 complex), −24.75 kcal/mol (top-2 complex), and −24.86 kcal/mol (top-3 complex). This study explored in silico screened phytochemicals against the main protease of the SARS-CoV-2 virus; however, the findings require an experimentally based study to further validate the obtained results. |
format | Online Article Text |
id | pubmed-9695405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96954052022-11-26 Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme Miandad, Khalid Ullah, Asad Bashir, Kashif Khan, Saifullah Abideen, Syed Ainul Shaker, Bilal Alharbi, Metab Alshammari, Abdulrahman Ali, Mahwish Haleem, Abdul Ahmad, Sajjad Molecules Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronaviruses that emerged in China at Wuhan city, Hubei province during December 2019. Subsequently, SARS-CoV-2 has spread worldwide and caused millions of deaths around the globe. Several compounds and vaccines have been proposed to tackle this crisis. Novel recommended in silico approaches have been commonly used to screen for specific SARS-CoV-2 inhibitors of different types. Herein, the phytochemicals of Pakistani medicinal plants (especially Artemisia annua) were virtually screened to identify potential inhibitors of the SARS-CoV-2 main protease enzyme. The X-ray crystal structure of the main protease of SARS-CoV-2 with an N3 inhibitor was obtained from the protein data bank while A. annua phytochemicals were retrieved from different drug databases. The docking technique was carried out to assess the binding efficacy of the retrieved phytochemicals; the docking results revealed that several phytochemicals have potential to inhibit the SARS-CoV-2 main protease enzyme. Among the total docked compounds, the top-10 docked complexes were considered for further study and evaluated for their physiochemical and pharmacokinetic properties. The top-3 docked complexes with the best binding energies were as follows: the top-1 docked complex with a −7 kcal/mol binding energy score, the top-2 docked complex with a −6.9 kcal/mol binding energy score, and the top-3 docked complex with a −6.8 kcal/mol binding energy score. These complexes were subjected to a molecular dynamic simulation analysis for further validation to check the dynamic behavior of the selected top-complexes. During the whole simulation time, no major changes were observed in the docked complexes, which indicated complex stability. Additionally, the free binding energies for the selected docked complexes were also estimated via the MM-GB/PBSA approach, and the results revealed that the total delta energies of MMGBSA were −24.23 kcal/mol, −26.38 kcal/mol, and −25 kcal/mol for top-1, top-2, and top-3, respectively. MMPBSA calculated the delta total energy as −17.23 kcal/mol (top-1 complex), −24.75 kcal/mol (top-2 complex), and −24.86 kcal/mol (top-3 complex). This study explored in silico screened phytochemicals against the main protease of the SARS-CoV-2 virus; however, the findings require an experimentally based study to further validate the obtained results. MDPI 2022-11-21 /pmc/articles/PMC9695405/ /pubmed/36432204 http://dx.doi.org/10.3390/molecules27228103 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Miandad, Khalid Ullah, Asad Bashir, Kashif Khan, Saifullah Abideen, Syed Ainul Shaker, Bilal Alharbi, Metab Alshammari, Abdulrahman Ali, Mahwish Haleem, Abdul Ahmad, Sajjad Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title | Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title_full | Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title_fullStr | Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title_full_unstemmed | Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title_short | Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme |
title_sort | virtual screening of artemisia annua phytochemicals as potential inhibitors of sars-cov-2 main protease enzyme |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695405/ https://www.ncbi.nlm.nih.gov/pubmed/36432204 http://dx.doi.org/10.3390/molecules27228103 |
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