Computational study of interaction of calixarene with ebola virus structural proteins and its potential therapeutic implications

Abstract

Ebola virus (EBOV) is a negative-strand RNA virus that causes hemorrhagic fever and fatal illness in humans. According to WHO, the Ebola virus caused 28,646 fatal cases and 11,323 deaths in West Africa due to hemorrhagic fever and deadly disease in humans between 2013 and 2016. Between 1976 and 2022, approximately 15,409 fatalities caused by EBOV took place worldwide. Unfortunately, no effective vaccine or drugs are available to prevent this deadly disease. In the present study, State-of-the-art tools based on in-silico methods were used to elucidate the interaction pattern of calixarene (CAL) with seven EBOV structural proteins, i.e., GP1,2, nucleoprotein (NP), polymerase cofactor (VP35), (VP40), transcription activator (VP30), VP24, and RNA-dependent RNA polymerase (L). CAL is a cage-like compound with supramolecular features. The molecular docking lead analysis using AutoDock tool has been performed to find out the binding pattern of CAL with EBOV proteins. Obtained results revealed efficient inhibitory properties of calixarene (CAL) against seven Ebola virus structural proteins i.e., GP1,2, nucleoprotein (NP), polymerase cofactor (VP35), (VP40), transcription activator (VP30), VP24, and RNA-dependent RNA polymerase (L). Molecular docking analysis shows that the interaction of CAL with VP24 was highest with the total binding energy -12.47 kcal/mol and 26.90 nM inhibitions constant. Molecular Dynamics study has also quantified the efficiency of CAL against VP24. In conclusion, the present study suggests that CAL and its derivatives could be used as inhibitors to counter EBOV infection. Furthermore, in vitro and in vivo laboratory experimentation is required to establish CAL and its derivatives as a potential inhibitor against EBOV.

Keywords: Calixarene; Ebola virus; Human health; In silico; Molecular docking simulation; Molecular dynamics simulation; VP40 matrix protein.