Molecular Docking Analysis of Designed Ligands on VP40 of Ebola Virus

Abstract

Ebola virus consists of different structural proteins, each of which plays its roles in different aspects of the viral life cycle. Among them, VP40 plays a number of critical roles in the viral lifecycle such as regulating viral transcription and coordinating virion assembly and budding from infected cells. Due to the fact that VP40 plays a vital role in the Ebola virus life cycle, it is considered as a promising target for the treatment of Ebola virus infection. This study aims to design ligands that have the potential to inhibit the VP40-RNA binding site. A total of seventeen ligands were designed based on the modification Q-88 (ZINC ID: 1342431) scaffold. Q-88 gave the best binding free energy of -97.27 kJ/mol and docking score of -7.1 kcal/mol according to previous literature. The seventeen ligands were then simulated against the RNA binding site using AutoDock Vina. The results showed that all ligands hold high binding affinities with VP40 ranging from -5.5 kcal/mol to -6.9 kcal/mol. Additionally, Q-88 was redocked as reference to determine if the modified ligands can surpass the binding affinity of Q-88 under the same circumstance. This study revealed that the modification of chlorine atoms on the benzene group did not give much effect towards increasing the binding affinity of the complex. Therefore, it is suggested that further chemical modifications should be carried out based on the Q-88 scaffold without altering the chlorine atom in the benzene group of the compound.