Discovery of Potential Inhibitors for RNA-Dependent RNA Polymerase of Norovirus: Virtual Screening, and Molecular Dynamics
Abstract
:1. Introduction
2. Results and Discussion
2.1. Binding Mode of the CMX521 and Ribavirin—MNV RdRp Complex
2.2. Binding Mode of the CID-122178506—MNV RdRp Complex
2.3. Binding Mode of the CID-57930781—MNV RdRp Complex
2.4. Binding Mode of the CID-16723073—MNV RdRp Complex
2.5. Binding Mode of the CID-472632—MNV RdRp Complex
2.6. Binding Mode of the CID-44396095—MNV RdRp Complex
3. Material and Methods
3.1. Data Software and Visualization
3.2. Dataset and Compound Library Preparation
3.3. Ligand Preparation
3.4. Receptor Preparation and Grid Generation
3.5. Structure-Based Virtual Screening
3.5.1. High Throughput Virtual Screening
3.5.2. E-Pharmacophore Hypothesis Generation and Database Screening
3.5.3. Extra Precision Docking (XP)
3.6. Molecular Dynamics Simulations
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Glide Score(kcal/mol) | Fitness Score | Prime MM-GBSA (dG bind kcal/mol) |
---|---|---|---|
CID-122178506 | −7.073 | 2.356 | −62.554 |
CID-57930781 | −7.587 | 2.336 | −62.528 |
CID-16723073 | −6.901 | 2.326 | −53.900 |
CID-472632 | −7.720 | 2.201 | −59.285 |
CID-44396095 | −7.390 | 2.118 | −61.969 |
Compound Identifier | MW | SASA | HBA | HBD | PSA | RO5 |
---|---|---|---|---|---|---|
CID-122178506 | 276.29 | 492.310 | 7.6 | 5 | 111.360 | 0 |
CID-57930781 | 262.27 | 478.545 | 7.6 | 5 | 111.298 | 0 |
CID-16723073 | 280.258 | 482.612 | 7.6 | 5 | 112.376 | 0 |
CID-472632 | 277.28 | 489.838 | 9.1 | 5 | 128.212 | 0 |
CID-44396095 | 283.24 | 484.955 | 7.4 | 4 | 109.498 | 0 |
CMX521 | 323.308 | 542.358 | 11.8 | 7 | 169.66 | 1 |
Entry | QPpolrz | QPlogPw | QPlogPo/w | QPlogS | QPlogHERG | QPPCaco | QPlogBB | QPlogKp | QPlogKhsa | HOR | QPPMDCK |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 25.008 | 16.812 | −0.252 | −2.033 | −4.173 | 78.500 | −1.721 | −4.552 | −0.650 | 2 | 31.611 |
2 | 24.349 | 17.097 | −0.366 | −2.034 | −4.319 | 95.715 | −1.591 | −4.399 | −0.675 | 2 | 39.166 |
3 | 24.727 | 16.87 | −0.128 | −2.264 | −4.069 | 100.678 | −1.446 | -4.478 | −0.636 | 3 | 70.187 |
4 | 25.164 | 18.530 | −0.953 | −2.065 | −4.036 | 39.974 | −1.927 | −5.314 | −0.720 | 2 | 15.242 |
5 | 25.376 | 15.542 | 0.081 | −2.815 | −4.172 | 97.571 | −1.308 | −4.766 | −0.549 | 3 | 102.922 |
6 | 28.005 | 24.005 | −1.897 | −2.282 | −4.182 | 14.282 | −2.542 | −6.261 | −0.873 | 2 | 5.011 |
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Ebenezer, O.; Jordaan, M.A.; Damoyi, N.; Shapi, M. Discovery of Potential Inhibitors for RNA-Dependent RNA Polymerase of Norovirus: Virtual Screening, and Molecular Dynamics. Int. J. Mol. Sci. 2021, 22, 171. https://doi.org/10.3390/ijms22010171
Ebenezer O, Jordaan MA, Damoyi N, Shapi M. Discovery of Potential Inhibitors for RNA-Dependent RNA Polymerase of Norovirus: Virtual Screening, and Molecular Dynamics. International Journal of Molecular Sciences. 2021; 22(1):171. https://doi.org/10.3390/ijms22010171
Chicago/Turabian StyleEbenezer, Oluwakemi, Maryam A. Jordaan, Nkululeko Damoyi, and Michael Shapi. 2021. "Discovery of Potential Inhibitors for RNA-Dependent RNA Polymerase of Norovirus: Virtual Screening, and Molecular Dynamics" International Journal of Molecular Sciences 22, no. 1: 171. https://doi.org/10.3390/ijms22010171