Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies
Abstract
:1. Introduction
2. Results
2.1. Drug-Likeness and ADMET Analysis of Compounds 1–10
2.2. Explanation of Active Sites in 3CLPro and PLPro
2.3. Validation of Docking Protocol with 3CLPro and PLPro
2.4. Non-Covalent Docking of Compounds 1–10 with 3CLPro
2.5. Non-Covalent Docking of Compounds 1–10 PLPro
2.6. Covalent Docking of Compounds 1–10 3CLPro
2.7. Covalent Docking of Compounds 1–10 with PLPro
2.8. MD Simulation Analysis
2.8.1. Root-Mean-Square-Deviation (RMSD) of Compounds 7, 8, and 9 with 3CLPro and PLPro
2.8.2. Root-Mean-Square-Fluctuation (RMSF) of Compounds 7, 8, and 9 with 3CLPro and PLPro
2.8.3. Radius of Gyration (Rg) of Compounds 7, 8, and 9 with 3CLPro and PLPro
3. Discussion
4. Materials and Methods
4.1. Phytochemicals from Medicinal Plants
4.2. Drug-Likeness and ADMET Properties
4.3. Ligand Preparation
4.4. Target Protein Preparation
4.5. Docking Experiments
4.5.1. Validation of Docking
4.5.2. Non-Covalent Docking
4.5.3. Covalent Docking
4.6. Molecular Dynamics (MD) Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound Code | Compound Name | 2D Structure | Name of Plants |
---|---|---|---|
1 | 5,3′,4′-trihydroxyflavan 7-O-gallate | Oncocalyx glabratus | |
2 | 5,4′-dihydroxyflavan 7-3′-O-digallate | Oncocalyx glabratus | |
3 | 5,3′-dihydroxyflavan 7-4′-O-digallate | Oncocalyx glabratus | |
4 | Spinasterol | Baccharoides schimperi | |
5 | Stigmasterol | Baccharoides schimperi | |
6 | 3′,4′,5,7-tetrahydroxy-3-methoxyflavone | Baccharoides schimperi | |
7 | Vernolepin | Baccharoides schimperi | |
8 | Vernodalol | Baccharoides schimperi | |
9 | 11β,13-dihydrovernodalin | Baccharoides schimperi | |
10 | Quercitrin 3-O-rhamnoside | Euphorpia schimperi |
Compound Code | A LogP | Mol. Wt. | nHBA | nHBD | MFPSA | Num-Ring | No. R. Bonds | TPSA | MR |
---|---|---|---|---|---|---|---|---|---|
1 | 4.178 | 410.374 | 8 | 5 | 0.364 | 4 | 4 | 136.68 | 105.42 |
2 | 5.126 | 562.478 | 12 | 7 | 0.401 | 5 | 7 | 203.44 | 140.87 |
3 | 5.126 | 562.478 | 12 | 7 | 0.401 | 5 | 7 | 203.44 | 140.87 |
4 | 7.639 | 412.691 | 1 | 1 | 0.042 | 4 | 5 | 20.23 | 128.69 |
5 | 7.639 | 412.691 | 1 | 1 | 0.042 | 4 | 5 | 20.23 | 128.69 |
6 | 1.856 | 316.262 | 7 | 4 | 0.397 | 3 | 2 | 120.36 | 82.50 |
7 | 0.818 | 276.285 | 5 | 1 | 0.273 | 3 | 1 | 72.83 | 66.87 |
8 | 0.892 | 392.4 | 8 | 2 | 0.291 | 2 | 8 | 119.36 | 95.00 |
9 | 1.236 | 362.374 | 7 | 1 | 0.275 | 3 | 5 | 99.13 | 86.88 |
10 | 0.589 | 448.377 | 11 | 7 | 0.462 | 4 | 3 | 190.28 | 103.90 |
Compound Code | HIA Level | CYP2D6 | Hepatotoxicity | PPB | Solubility Level | Molar Solubility Log(sw) | BBBP Level | AlogP98 | PSA_2D |
---|---|---|---|---|---|---|---|---|---|
1 | 2 | True | False | False | 2 | −5.103 | 4 | 4.178 | 139.238 |
2 | 3 | True | False | False | 1 | −7.249 | 4 | 5.126 | 207.1 |
3 | 3 | True | False | False | 1 | −7.127 | 4 | 5.126 | 207.1 |
4 | 3 | True | False | True | 1 | −7.962 | 4 | 7.639 | 20.815 |
5 | 3 | False | False | True | 1 | −7.963 | 4 | 7.639 | 20.815 |
6 | 0 | True | False | False | 3 | −2.93 | 4 | 1.856 | 118.422 |
7 | 0 | False | False | True | 3 | −2.392 | 3 | 0.818 | 73.277 |
8 | 0 | False | False | True | 3 | −2.065 | 4 | 0.893 | 120.323 |
9 | 0 | False | False | True | 3 | −2.842 | 3 | 1.236 | 99.508 |
10 | 3 | False | False | False | 3 | −3.888 | 4 | 0.589 | 189.799 |
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Saquib, Q.; Bakheit, A.H.; Ahmed, S.; Ansari, S.M.; Al-Salem, A.M.; Al-Khedhairy, A.A. Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies. Molecules 2024, 29, 998. https://doi.org/10.3390/molecules29050998
Saquib Q, Bakheit AH, Ahmed S, Ansari SM, Al-Salem AM, Al-Khedhairy AA. Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies. Molecules. 2024; 29(5):998. https://doi.org/10.3390/molecules29050998
Chicago/Turabian StyleSaquib, Quaiser, Ahmed H. Bakheit, Sarfaraz Ahmed, Sabiha M. Ansari, Abdullah M. Al-Salem, and Abdulaziz A. Al-Khedhairy. 2024. "Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies" Molecules 29, no. 5: 998. https://doi.org/10.3390/molecules29050998
APA StyleSaquib, Q., Bakheit, A. H., Ahmed, S., Ansari, S. M., Al-Salem, A. M., & Al-Khedhairy, A. A. (2024). Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies. Molecules, 29(5), 998. https://doi.org/10.3390/molecules29050998