Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing
Abstract
:1. Introduction
2. Results
2.1. Structure Retrieval of Spike Protein
2.2. Database Screening and Docking Study
2.3. Drug-Likeness/ADMET Profiling
2.4. Biochemical Classification of Idetified Compounds
2.5. Energy Calculations
2.6. MD Simulation
2.6.1. Root Mean Square Deviation (RMSD)
2.6.2. Root Mean Square Fluctuations
2.6.3. Solvent Accessible Surface Area (SASA)
2.6.4. Water Bridges, Ionic Interactions and Hydrogen Bonding Graphs
3. Discussion
4. Materials and Methods
4.1. Data Collection and Ligand Database
4.2. Receptor Preparation and Analysis of Target Active Binding Sites
4.3. Molecular Docking
4.4. Analysis of Ligand Receptor Interaction
4.5. Physiochemical Property Profile and Toxicity Prediction
4.6. MM-GBSA Binding Free Energy Calculations
4.7. Molecular Dynamic Simulation
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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IDs (PubChem) | Phytochemicals | Binding Affinity (kcal/mol) | RMSD Value | Hydrogen Bonds and Other Interacting Residues |
---|---|---|---|---|
457885 | Phylloflavan | −14.09 | 0.59 | Tyr 455; Tyr 550; Arg 393; Gly 596; Tyr 453; Arg 403 |
1548994 | Milk thistle | −13.10 | 1.01 | Tyr 453; Tyr 553; Arg 493; His 39 |
102394711 | Ilexin B | −13.04 | 1.53 | Tyr 453; Gly 496; His 34; Arg 403 |
10885340 | Isosilybin B | −12.19 | 0.92 | Arg 390; Arg 434; Lys 330; His 39 Gly 596 |
Sr No | Compounds Name | Log P | M Weight | HBD | HBA |
---|---|---|---|---|---|
1 | Phylloflavan | 2.53 | 498.48 | 10 | 4 |
2 | Milk thistle | −1.25 | 481.43 | 10 | 4 |
3 | Ilexin B | −1.82 | 464 | 10 | 2 |
4 | Isosilybin B | −1.25 | 481.43 | 10 | 4 |
Compounds | Phylloflavan | Milk Thistle | Ilexin B | Isosilybin B |
---|---|---|---|---|
Absorption | ||||
Blood-Brain Barrier | No | No | No | No |
Distribution | ||||
Gastro-Intestinal-Absorption | Low | Low | Low | Low |
P-glycoprotein-substrate | No | No | Yes | No |
CYP450-1A2-Inhibitor | No | No | No | No |
Metabolisum | ||||
CYP450-2C9-Inhibitor | No | No | No | No |
CYP450-2D6-Inhibitor | No | No | No | No |
CYP450-2C19-Inhibitor | No | No | Yes | No |
CYP450-3A4 Inhibitor | No | No | No | No |
Toxicity | ||||
Cytotoxicity | Non-toxic | Non-toxic | Non-toxic | Non-toxic |
Immunogenicity | Non-toxic | Non-toxic | Non-toxic | Non-toxic |
Mutagenicity | Non-toxic | Non-toxic | Non-toxic | Non-toxic |
Compounds | Taxonomy | Classification | Diseases |
---|---|---|---|
Phylloflavan | Phyllocladus trichomanoides Phyllocladus alpinus | Polyketides Flavonoids Flavans, Flavanols and Leucoanthocyanidins | Antileishmanial activity and modulatory effects on nitric oxide and tumor necrosis human immunodeficiency virus type 1 integrase |
Milk thistle | Anastatica hierochuntica Silybum marianum Aspergillus iizukae | Flavonoids silibinin dehydrosilibinin silychristin silydianin | Liver disorders and gallbladder problems.hepatitis, cirrhosis, jaundice, diabetes, indigestion |
Ilexin B | Panax notoginseng | Glucosides Carbohydrates | Inflammatory bowel disease, arthritis, ischemia, atherosclerosis, Alzheimer disease and trauma, as well as hyperlipidemia, diabetes |
Isosilybin B | Anastatica hierochuntica Silybum marianum | Hydrocarbons, Aromatic Hydrocarbons, Cyclic Benzene Derivatives Flavonolignans | Antiprostate cancer activity via inhibiting proliferation and inducing G1 phase arrestand apoptosia. |
Energy Parameters | VDWAALS (kcal mol−1) | Delta G Gas (kcal mol−1) | Delta g Solv (kcal mol−1) | Delta Total (kcal mol−1) |
---|---|---|---|---|
Phylloflavan/S-RBD | −29.50 | −34.56 | 8.21 | −30.35 |
Milk thistle/S-RBD | −30.61 | −31.87 | 9.86 | −28.90 |
Ilexin B/S-RBD | −31.70 | −29.54 | 10.23 | −31.83 |
Isosilybin B/S-RBD | −28.74 | −32.33 | 11.23 | −34.97 |
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Aloufi, B.H.; Snoussi, M.; Sulieman, A.M.E. Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing. Molecules 2022, 27, 2401. https://doi.org/10.3390/molecules27082401
Aloufi BH, Snoussi M, Sulieman AME. Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing. Molecules. 2022; 27(8):2401. https://doi.org/10.3390/molecules27082401
Chicago/Turabian StyleAloufi, Bandar Hamad, Mejdi Snoussi, and Abdel Moneim E. Sulieman. 2022. "Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing" Molecules 27, no. 8: 2401. https://doi.org/10.3390/molecules27082401