Computer-Aided Design of Lead Flavonoid Compounds Targeting VP35 for Marburg Virus Treatment

The Marburg virus, a highly infectious and severe hemorrhagic fever virus classified within the Filoviridae family alongside the Ebola virus, exhibits a notable mortality rate, frequently surpassing 50% during outbreaks. The pronounced pathogenicity of the disease renders it a substantial public health concern. The Marburg virus, akin to other filoviruses, presents challenges attributable to limited comprehension of its biology, transmission dynamics, and pathogenesis. A comprehensive understanding of these facets is imperative for the formulation of targeted therapeutic interventions. Significantly, there exists a dearth of licensed vaccines or antiviral therapies for the Marburg virus. The intricate nature of the virus, coupled with the necessity for stringent testing, complicates the development of effective vaccines and antiviral treatments. The ongoing endeavors to unravel the intricacies of the Marburg virus and devise efficacious countermeasures assume paramount importance in the realm of global health security. A variety of multidisciplinary methodologies aimed at accelerating and reducing the expenses associated with drug development have piqued the interest of researchers. Specifically, an evaluation of flavonoids against the Marburg virus protein was undertaken as a potential combat strategy against the infection. Upon identification of the protein target (VP35), molecular docking between flavonoids and the selected target was executed. Subsequent to this, an ADMET analysis was conducted to evaluate the pharmacokinetic properties. Based on the docking scores and ADMET test results, the most promising compound was selected. The primary objectives of this study centered on selecting a target protein and identifying lead compounds to combat the Marburg Virus. To achieve these, the VP35 pharmacological target (PDB ID: 4gh9) was identified through an extensive literature review. The three-dimensional structure was retrieved from the Protein Data Bank. Potential Druggable flavonoids underwent molecular docking using AutoDock Vina within Pyrx. The interactions between these chemical compounds and their respective target proteins were analyzed using BIOVIA Discovery Studio. Moreover, the stability of protein-inhibitor complexes in a physiological environment was evaluated through Molecular Dynamics Simulation (MD simulation) using Desmond and in-depth post MD simulation analysis. Our investigation divulges that Five compounds" CID 969516, CID 5280445, CID 5280343, CID 5280443, CID 5280863" displayed potential inhibitory effects against targeted protein, thereby impeding the virus's functionality. These compounds exhibited non-toxic properties, adhered to ADMET and blood-brain barrier (BBB) criteria, and demonstrated optimal interaction criteria. This discovery holds significant implications for broader research endeavors and could lead to the development of novel Therapeutic. The adept repurposing of these chemicals has shown efficiency as potential inhibitors while reducing adverse effects and enhancing efficacy.