Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach
Abstract
:1. Introduction
2. Material and Methods
2.1. Softwares Used in This Study
2.2. Chemical Library Dataset
2.3. Ligand Preparation
2.4. Receptor Preparation and Grid Generation
2.5. Virtual Screening and E-Pharmacophore Generation
2.6. Induced Fit Docking
2.7. Quantum Mechanical/Molecular Mechanical (QM-MM) Using Qsite
2.8. Molecular Dynamics Simulations
3. Results and Discussion
3.1. The Binding Pose of CMX521 and PPNDS—HNV RdRp Docked Complex
3.2. The Binding Pose of ZINC1617939–HNV RdRp Docked Complex
3.3. The Binding POSE of ZINC6425208–HNV RdRp Docked Complex
3.4. The Binding Pose of ZINC1642549–HNV RdRp Docked Complex
3.5. The Binding Poses of ZINC5887658 and ZINC32068149- HNV RdRp Docked Complex
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Entry | Compound ID | QPlogPw | QPlogPo/w | QPlogS | QPlogHERG | QPPCaco | QPlogBB | QPlogKp | QPlogKhsa | HOR |
---|---|---|---|---|---|---|---|---|---|---|
1 | ZINC1617939 | 12.889 | 1.000 | −2.603 | −5.463 | 6.582 | −2.253 | −7.077 | −0.638 | 2 |
2 | ZINC6425208 | 8.949 | 2.812 | −4.174 | −4.815 | 246.337 | −1.278 | −3.233 | −0.127 | 3 |
3 | ZINC1642549 | 15.413 | 1.320 | −2.842 | −4.503 | 223.103 | −1.449 | −5.618 | −0.368 | 3 |
4 | ZINC5887658 | 9.948 | 2.015 | −4.306 | −4.306 | 59.428 | −0.308 | −3.897 | −0.369 | 3 |
5 | ZINC32068149 | 19.353 | 2.339 | −4.137 | −5.539 | 144.709 | −0.420 | −4.708 | −0.227 | 3 |
Entry | Compound ID | Glide Score (kcal/mol) | Glide Emodel (kcal/mol) | Glide Energy (kcal/mol) | IFD Score (kcal/mol) |
---|---|---|---|---|---|
1 | ZINC1617939 | −13.027 | −81.298 | −60.302 | −1045.910 |
2 | ZINC6425208 | −9.226 | −52.870 | −38.120 | −1040.540 |
3 | ZINC1642549 | −9.003 | −81.682 | −54.214 | −1040.180 |
4 | ZINC5887658 | −9.744 | −50.500 | −45.429 | −1042.37 |
5 | ZINC32068149 | −10.507 | −67.805 | −50.600 | −1042.18 |
4 | CMX521 | −7.886 | −79.970 | −57.383 | −1041.660 |
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Ebenezer, O.; Damoyi, N.; Jordaan, M.A.; Shapi, M. Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach. Molecules 2022, 27, 380. https://doi.org/10.3390/molecules27020380
Ebenezer O, Damoyi N, Jordaan MA, Shapi M. Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach. Molecules. 2022; 27(2):380. https://doi.org/10.3390/molecules27020380
Chicago/Turabian StyleEbenezer, Oluwakemi, Nkululeko Damoyi, Maryam A. Jordaan, and Michael Shapi. 2022. "Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach" Molecules 27, no. 2: 380. https://doi.org/10.3390/molecules27020380