Comparison of the Binding Energies of Approved Mpox Drugs and Phytochemicals through Molecular Docking, Molecular Dynamics Simulation, and ADMET Studies: An In Silico Approach

Mohapatra, Ranjan K. and Mahal, Ahmed and Ansari, Azaj and Kumar, Manjeet and Guru, Jyoti Prakash and Sarangi, Ashish K. and Abdou, Aly and Mishra, Snehasish and Aljeldah, Mohammed and AlShehail, Bashayer M. and Alissa, Mohammed and Garout, Mohammed and Alsayyah, Ahmed and Alshehri, Ahmad A. and Saif, Ahmed and Alqahtani, Abdulaziz and Alshehri, Fahd A. and Alamri, Aref A. and Rabaan, Ali A. (2023) Comparison of the Binding Energies of Approved Mpox Drugs and Phytochemicals through Molecular Docking, Molecular Dynamics Simulation, and ADMET Studies: An In Silico Approach. Journal of Biosafety and Biosecurity, 5 (3). pp. 118-132. ISSN 25889338

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Abstract

The mpox (previously monkeypox) outbreak in more than 100 non-endemic countries in 2022 posed a serious global health concern. Mpox is emerging as a global public health threat from a seemingly neglected disease. A42R profilin-like protein from mpox virus (PDB ID: 4QWO) could be a preferred target lead. The binding affinity of commonly used drugs/mAbs (tecovirimat, brincidofovir, cidofovir) for A42R profilin-like protein was examined in silico through molecular docking. Further, the results were compared with those of the phytochemicals curcumin, rutin, and theaflavin. Tecovirimat (−7.31 kcal/mol, IC50 = 4.39 µM) and theaflavin (−6.99 kcal/mol, IC50 = 7.54 µM) had the highest affinities. Molecular dynamics simulation of the theaflavin–4QWO complex was performed to ascertain the stability of ligand–protein interactions in natural charge, molecular electrostatic potential, and frontier molecular orbital analyses. The predicted QSAR and pharmacokinetic properties of all compounds were evaluated to find a suitable candidate for designing and developing new drugs. The evaluated log P values for brincidofovir and tecovirimat were higher than those of the other drugs in the QSAR study. Theaflavin had an impressive log P of 4.77, which hints at its high biological activity. The findings recommend further in vitro experimental validation to develop potential low-cost mpox therapies.

Item Type: Article
Uncontrolled Keywords: ADMET, DFT, MD Simulation, Molecular Docking, Mpox, QSAR
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Department of Medical Biochemical Analysis > Research papers
Depositing User: ePrints Depositor
Date Deposited: 30 Oct 2024 17:12
Last Modified: 30 Oct 2024 17:12
URI: https://eprints.cihanuniversity.edu.iq/id/eprint/1969

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