In Silico Discovery of Small Molecule Modulators Targeting Ebola Virus VP 35 and VP 40 protein

AbstractEbola virus (EBoV) proteins VP35 and VP40 are acknowledged as significant pharmacological targets for disrupting viral replication, virion assembly, and the budding process from host cells. We employed molecular docking based throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking to discover candidate compounds. Subsequently, molecular dynamics simulations, and ADMET analyses to identify potential small molecular compounds that could inhibit the Ebola virus. Among 210,590 compounds from the SPECS database, we found the compounds AO-022/43452438, AN-465/43369333, and AN-465/43369198 were optimal candidates for the EBOV-VP35 protein, while AN-465/43369160, AN-465/4341136, and AN-465/43369952 also emerged as optimal compounds for the EBOV-VP40 protein. Furthermore, we employed the energy decomposition technique, MM-GB/SA, to identify the top ten amino acids that significantly contribute to the binding interactions. ADMET result implicated that the six compounds have potential druggability, but special attention should be given to AN-465/43369333 due to potential cardiac toxicity. In conclusions, the six compounds and their key interacting amino acid sites identified in this study may serve as a valuable platform for the future development of novel therapeutics targeting the Ebola virus.