SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein
The SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found t...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/1144 |
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| author | Aqsa Salamat Naveen Kosar Ayesha Mohyuddin Muhammad Imran Muhammad Nauman Zahid Tariq Mahmood |
| author_facet | Aqsa Salamat Naveen Kosar Ayesha Mohyuddin Muhammad Imran Muhammad Nauman Zahid Tariq Mahmood |
| author_sort | Aqsa Salamat |
| collection | DOAJ |
| description | The SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found to be likely candidates for the synthesis of novel therapeutic drug. In the past, proteins were capable of engaging in interaction with a wide variety of ligands, including both manmade and plant-derived small molecules. <i>Pyrus communis</i> L., <i>Ginko bibola</i>, <i>Carica papaya</i>, <i>Syrian rue</i>, and <i>Pimenta dioica</i> were some of the plant species that were studied for their tendency to interact with SARS-CoV-2 main protease (Mpro) in this research project (6LU7). This scenario investigates the geometry, electronic, and thermodynamic properties computationally. Assessing the intermolecular forces of phytochemicals with the targets of the SARS-CoV-2 Mpro spike protein (SP) resulted in the recognition of a compound, kaempferol, as the most potent binding ligand, −7.7 kcal mol<sup>−1</sup>. Kaempferol interacted with ASP-187, CYS-145, SER-144, LEU 141, MET-165, and GLU-166 residues. Through additional molecular dynamic simulations, the stability of ligand–protein interactions was assessed for 100 ns. GLU-166 remained intact with 33% contact strength with phenolic OH group. We noted a change in torsional conformation, and the molecular dynamics simulation showed a potential variation in the range from 3.36 to 7.44 against a 45–50-degree angle rotation. SAR, pharmacokinetics, and drug-likeness characteristic investigations showed that kaempferol may be the suitable candidate to serve as a model for designing and developing new anti-COVID-19 medicines. |
| first_indexed | 2024-04-25T00:23:58Z |
| format | Article |
| id | doaj.art-ff3475c0e7184b829df9f41386d263b9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:23:58Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ff3475c0e7184b829df9f41386d263b92024-03-12T16:51:15ZengMDPI AGMolecules1420-30492024-03-01295114410.3390/molecules29051144SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike ProteinAqsa Salamat0Naveen Kosar1Ayesha Mohyuddin2Muhammad Imran3Muhammad Nauman Zahid4Tariq Mahmood5Department of Chemistry, University of Management and Technology (UMT), C-II, Johar Town, Lahore 54770, PakistanDepartment of Chemistry, University of Management and Technology (UMT), C-II, Johar Town, Lahore 54770, PakistanDepartment of Chemistry, University of Management and Technology (UMT), C-II, Johar Town, Lahore 54770, PakistanDepartment of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi ArabiaDepartment of Biology, College of Science, University of Bahrain, Sakhir P.O. Box 32038, BahrainDepartment of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, PakistanThe SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found to be likely candidates for the synthesis of novel therapeutic drug. In the past, proteins were capable of engaging in interaction with a wide variety of ligands, including both manmade and plant-derived small molecules. <i>Pyrus communis</i> L., <i>Ginko bibola</i>, <i>Carica papaya</i>, <i>Syrian rue</i>, and <i>Pimenta dioica</i> were some of the plant species that were studied for their tendency to interact with SARS-CoV-2 main protease (Mpro) in this research project (6LU7). This scenario investigates the geometry, electronic, and thermodynamic properties computationally. Assessing the intermolecular forces of phytochemicals with the targets of the SARS-CoV-2 Mpro spike protein (SP) resulted in the recognition of a compound, kaempferol, as the most potent binding ligand, −7.7 kcal mol<sup>−1</sup>. Kaempferol interacted with ASP-187, CYS-145, SER-144, LEU 141, MET-165, and GLU-166 residues. Through additional molecular dynamic simulations, the stability of ligand–protein interactions was assessed for 100 ns. GLU-166 remained intact with 33% contact strength with phenolic OH group. We noted a change in torsional conformation, and the molecular dynamics simulation showed a potential variation in the range from 3.36 to 7.44 against a 45–50-degree angle rotation. SAR, pharmacokinetics, and drug-likeness characteristic investigations showed that kaempferol may be the suitable candidate to serve as a model for designing and developing new anti-COVID-19 medicines.https://www.mdpi.com/1420-3049/29/5/1144COVID-19density functional theory (DFT)molecular docking (MD)molecular dynamics simulationstructure–activity relationship (SAR)pharmacokinetics |
| spellingShingle | Aqsa Salamat Naveen Kosar Ayesha Mohyuddin Muhammad Imran Muhammad Nauman Zahid Tariq Mahmood SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein Molecules COVID-19 density functional theory (DFT) molecular docking (MD) molecular dynamics simulation structure–activity relationship (SAR) pharmacokinetics |
| title | SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein |
| title_full | SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein |
| title_fullStr | SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein |
| title_full_unstemmed | SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein |
| title_short | SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein |
| title_sort | sar molecular docking and molecular dynamic simulation of natural inhibitors against sars cov 2 mpro spike protein |
| topic | COVID-19 density functional theory (DFT) molecular docking (MD) molecular dynamics simulation structure–activity relationship (SAR) pharmacokinetics |
| url | https://www.mdpi.com/1420-3049/29/5/1144 |
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