Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease
Abstract
:1. Introduction
2. Results
2.1. ADME/Tox Prediction
2.2. Docking Calculations
2.3. Molecular Dynamic Simulation
3. Discussion
3.1. Drug-Likeness (ADME/Tox) Analysis
3.2. Docking Analysis
3.3. Molecular Dynamic Simulation
4. Materials and Methods
4.1. ADME/Tox Analysis (Drug-Likeness)
4.2. Protein Preparation
4.3. Ligand Selection and Preparation
4.4. Molecular Docking Calculation
4.5. ∆G Energy Calculation of the Docked Complexes
4.6. Molecular Dynamics Simulation (MDs)
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | ID a | M.W b | ROF c | QplogHERG d | QplogPoW e | QplogKP f | Donor HB | Acceptor HB | QplogS g | QplogBB h |
---|---|---|---|---|---|---|---|---|---|---|
Quercetin 3-O-Neohesperidoside | 5748416 | 610.5 | 2 | −6.449 | −1.998 | −6.423 | 9 | 20.55 | −2.932 | −4.728 |
Myricetin 3-Rutinoside | 44259428 | 626.5 | 2 | −6.394 | −2.455 | −5.583 | 10 | 21.3 | −2.341 | −4.306 |
Quercetin 3-Rhamnoside | 5353915 | 448.3 | 2 | −5.451 | −0.55 | −6.101 | 6 | 12.05 | −3.196 | −3.312 |
Rutin | 5280805 | 610.5 | 2 | −5.238 | −2.495 | −7.251 | 9 | 20.55 | −2.175 | −4.503 |
Myricitrin | 5281673 | 464.3 | 2 | −5.463 | −1.045 | −6.589 | 7 | 12.8 | −2.779 | −3.48 |
Compound | ID | Ames Toxicity | Carcinogens | Acute Oral Toxicity | Rat Acute Toxicity |
---|---|---|---|---|---|
Quercetin 3-O-Neohesperidoside | 5748416 | AT | NC | III | 2.2619 |
Myricetin 3-Rutinoside | 44259428 | NAT | NC | III | 2.4984 |
Quercetin 3-Rhamnoside | 5353915 | NAT | NC | III | 2.5458 |
Rutin | 5280805 | NAT | NC | III | 2.4984 |
Myricitrin | 5281673 | NAT | NC | III | 2.5458 |
Name | Dock Score | ∆G Bind | H-Bond | Residues (Å) | Other Bond (Å) |
---|---|---|---|---|---|
Standard | −16.5 | −80.88 | 6 | CYS145 (2.13), LEU141 (2.76), PHE140 (2.02), GLU166 (1.68,1.83, 2.05) | Salt bridges (2) |
Quercetin 3-O-Neohesperidoside | −16.8 | −87.60 | 5 | GLY143 (2.76), CYS145 (2.11), GLN189 (2.11), THR190 (1.76), HIS41 (2.30) | π-π stacking HIS41 (1.49) |
Myricetin 3-Rutinoside | −12.9 | −87.50 | 7 | CYS145 (2.08), ASN142 (1.75), GLU166 (1.98), THR190 (2.21), ARG188 (1.97), HIS164 (1.90,1.98) | |
Quercetin 3-Rhamnoside | −10.3 | −80.17 | 4 | LEU141 (1.49), THR190 (1.78), GLU166 (2.01), HIS164 (1.81) | |
Rutin | −10.0 | −58.95 | 6 | THR190 (1.83), HIS41 (2.08), GLY143 (2.39,1.89), ASN142 (1.92), LEU141 (2.10) | - |
Myricitrin | −9.1 | −49.22 | 3 | CYS145 (2.51), ASN142 (2.04), THR190 (1.83) | π-π stacking HIS41 (5.37) |
Properties | A | B | C | D | E |
---|---|---|---|---|---|
RMSD | 1.98 ± 0.19 | 2.25 ± 0.26 | 3.05 ± 0.57 | 1.81 ± 0.30 | 2.26 ± 0.51 |
RMSF | 1.00 ± 0.51 | 1.31 ± 0.55 | 1.27 ± 0.58 | 1.15 ± 0.58 | 1.25 ± 0.65 |
rGyr | 5.03 ± 0.09 | 4.96 ± 0.03 | 4.57 ± 0.05 | 5.15 ± 0.10 | 6.09 ± 0.09 |
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Fadaka, A.O.; Sibuyi, N.R.S.; Martin, D.R.; Klein, A.; Madiehe, A.; Meyer, M. Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease. Int. J. Mol. Sci. 2021, 22, 9431. https://doi.org/10.3390/ijms22179431
Fadaka AO, Sibuyi NRS, Martin DR, Klein A, Madiehe A, Meyer M. Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease. International Journal of Molecular Sciences. 2021; 22(17):9431. https://doi.org/10.3390/ijms22179431
Chicago/Turabian StyleFadaka, Adewale Oluwaseun, Nicole Remaliah Samantha Sibuyi, Darius Riziki Martin, Ashwil Klein, Abram Madiehe, and Mervin Meyer. 2021. "Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease" International Journal of Molecular Sciences 22, no. 17: 9431. https://doi.org/10.3390/ijms22179431