Virtual Screening Based on Docking and Molecular Dynamics Simulations of Potential Ebola Receptor Inhibitors

Abstract Galidesivir (BCX4430) is known to treat different viruses under Filoviridae family and it has proved as a potential antiviral drug against Ebola virus. Therefore, for treating Ebola virus in particular there is a need for the identification a drug compound. In this work, derivatives of Pyrrolopyrimidine are designed to investigate their antiviral activity against Ebola virus receptors (VP24, VP30, VP35 and VP40). FBDD‐based virtual screening resulted in eight compounds, based on pharmacokinetics and Density Functional Theory (DFT) analysis; four compounds were shortlisted. Further, docking simulation resulted that, compound 4 exhibited −9.8, −9.6, −9.7, −9.5 kcal/mol binding energy against each Ebola receptor, respectively. The predicted docking results of the above compound against each receptor were better than BCX4430. Docking results were validated and compared to BCX4430 by performing Molecular Dynamic simulations at 100 ns, in order to study the Root Mean Square Deviation, Root Mean Square Fluctuation, Radius of Gyration and MM/PBSA of the docked complexes. Therefore, the study lays the foundation for the designed and screened compound to act as a probable drug compound against Ebola.