Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study
Abstract
:1. Introduction
2. Results and Discussion
2.1. Determination of Antiviral Activity Using Molecular Docking
2.2. Pharmacophore Evaluation
3. Materials and Methods
3.1. Origin of Compounds
3.2. Molecular Docking
3.3. 3D Pharmacophore Model Generation
4. 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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Compounds (Pubchem ID) | Docking Score (−) (kcal/mol) | Docking Score (−) (kcal/mol) | Docking Score (−) (kcal/mol) |
---|---|---|---|
PDB ID: 2V54 | PDB ID: 4QWO | PDB ID: 6BED | |
(Thymidylate Kinase) | (A42R Profilin) | (D13 Protein) | |
MXN (4212) (Standard) | 6.9 | 6.7 | 7.3 |
(1) (13276605) | 7.2 | 6.6 | 7.9 |
(2) (153640723) | 7.2 | 6.8 | 8 |
(3) (44275839) | 6.7 | 6.4 | 7.6 |
(4) (71044822) | 6.9 | 6.6 | 7.3 |
(5) (142963046) | 6.9 | 6.1 | 7.3 |
(6) (44316536) | 6.8 | 6.2 | 7.5 |
(7) (24848320) | 6.9 | 6.8 | 7.4 |
(8) (59835539) | 7.2 | 6 | 7.9 |
(9) (44541200) | 7 | 6.1 | 7.4 |
(10) (58102019) | 7 | 6.8 | 7.5 |
(11) (143270488) | 7.2 | 6.6 | 7.4 |
(12) (145293737) | 7 | 6.8 | 8.3 |
(13) (44541201) | 6.8 | 6.3 | 7.5 |
Residues | MXN | Compound (2) | Compound (7) | Compound (10) | Compound (12) |
---|---|---|---|---|---|
Arg41(B) | x | x | xx | x | x |
Arg93(B) | xx | x | xx | xx | xx |
Asn37(B) | xx | xx | xx | x | xx |
Asp13(B) | xx | xx | xx | xx | |
Asp92(B) | xx | x | x | ||
Glu142(B) | xx | xx | x | x | xx |
Glu145(B) | x | xx | x | x | |
Gly16(B) | x | x | x | x | |
Leu53(B) | x | x | x | x | |
Lys14(B) | x | xx | x | x | x |
Lys17(B) | x | x | x | x | x |
Phe38(B) | x | ||||
Phe68(B) | x | x | |||
Pro39 (B) | x | ||||
Ser15(B) | xx | xx | xx | x | |
Ser97(B) | xx | ||||
Thr18(B) | xx | xx | x | xx | x |
Tyr35(B) | x | ||||
Tyr101(B) | x | x | x | x | |
Tyr144(B) | x | x | x | x |
Residues | MXN | Compound (2) | Compound (7) | Compound (10) | Compound (12) |
---|---|---|---|---|---|
Ala129(B) | x | x | x | ||
Ala130(B) | x | x | x | x | |
Arg119(A) | x | x | x | x | x |
Arg127(A) | x | x | x | x | |
Arg129(B) | x | ||||
Asn14(A) | xx | xx | xx | xx | xx |
Asn78(B) | x | x | x | x | x |
Asp10(A) | x | x | x | x | x |
Asp116(A) | x | x | x | x | x |
Asp123(A) | x | x | x | x | x |
Glu77(B) | x | xx | x | x | |
His100(B) | x | x | |||
Lys16(A) | x | x | x | x | x |
Phe17(A) | x | x | x | x | x |
Thr120(A) | xx | xx | x | xx | x |
Thr126(B) | x | x | |||
Tyr80(B) | x | x |
Residues | MXN | Compound (2) | Compound (7) | Compound (10) | Compound (12) |
---|---|---|---|---|---|
Asn117(A) | x | xx | x | x | x |
Asn118(A) | xx | x | x | x | xx |
Asn121(A) | xx | x | xx | xx | xx |
Asn464(A) | xx | xx | xx | xx | |
Asn530(A) | xx | xx | x | x | x |
Glu114(A) | x | xx | x | x | |
Glu230(A) | x | xx | xx | ||
Gly473(A) | x | ||||
Ile110(A) | x | ||||
Lys159(A) | xx | xx | xx | xx | |
Lys484(A) | x | x | x | ||
Pro161(A) | x | x | x | ||
Pro232(A) | x | x | x | ||
Ser254(A), | x | x | x | x | x |
Ser256(A) | x | x | xx | xx | xx |
Ser470(A) | x | ||||
Thr468(A) | x | x | x | ||
Thr474(A) | xx | xx | xx | x | |
Thr464(A) | x | xx | |||
Thr468(A) | x | x | |||
Trp108(A) | xx | x | x | ||
Val528(A) | x | x |
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Preet, G.; Oluwabusola, E.T.; Milne, B.F.; Ebel, R.; Jaspars, M. Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study. Int. J. Mol. Sci. 2022, 23, 14287. https://doi.org/10.3390/ijms232214287
Preet G, Oluwabusola ET, Milne BF, Ebel R, Jaspars M. Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study. International Journal of Molecular Sciences. 2022; 23(22):14287. https://doi.org/10.3390/ijms232214287
Chicago/Turabian StylePreet, Gagan, Emmanuel T. Oluwabusola, Bruce Forbes Milne, Rainer Ebel, and Marcel Jaspars. 2022. "Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study" International Journal of Molecular Sciences 23, no. 22: 14287. https://doi.org/10.3390/ijms232214287