Investigation of the New Inhibitors by Modified Derivatives of Pinocembrin for the Treatment of Monkeypox and Marburg Virus With Different Computational Approaches

Abstract

The widespread occurrence of Monkeypox and Marburg virus fatalities all over the globe has prompted biologists, pharmacologists, chemists, and pharmacists to develop potent drug agents. This study generated eight compounds from pinocembrin derivatives by adding different functional groups to identify new effective drugs against Monkeypox and Marburg virus. Before the computational screening, they were optimized by material studio 08 in Density Functional Theory (DFT). Then, the "Highest Occupied Molecular Orbital" (HOMO), and the "Lowest Unoccupied Molecular Orbital" (LUMO) were analyzed, which further turned into the measurement of the chemical reactivity such as E(gap), hardness, softness, electronegativity, index, and chemical potential, between them. All the compounds were documented to have a greater hardness and softness index. After that, sequentially, Lipinski rule analysis, molecular docking, acute toxicity, acute systemic toxicity, Quantitative Structure-Activity Relationships (QSAR), and PASS prediction were all performed on these molecules to establish a potent medication. Firstly, the PASS prediction spectrum was taken, and these derivatives are highly potent antiviral compared with antibacterial, antifungal, and antidiabetics. The binding energy was determined using the PyRx AutoDock vina technique to identify the intermolecular protein- ligand couplings. The presentable maximum binding affinities were -9.0 kcal/mole against the Monkeypox virus (PDB ID 4QWO), and the top score against the Marburg virus (PDB 4OR8) was -8.3 kcal/mole. The pIC50 score ranges from 4.44 to 4.44 for the reported molecules. Finally, the pharmacokinetics showed that most of the ligands are free from carcinogenic effects, have better absorbance capability, have low to moderate aqueous solubility, and are ligands 01, 03, 04, 05, and 08 might penetrate the blood-brain barrier (BBB). The pinocembrin derivatives exhibited significant structural and pharmacological features and can be used as prospective antiviral medicines for Monkeypox and Marburg viruses. However, a more experimental investigation is required on a broad scale to establish them as commercial medications