Dronabinol as an answer to flavivirus infections: an in-silico investigation

Abstract

Flavivirus infections are common in several parts of the world. Two major types of flaviviruses are dengue and zika viruses. Both these two viral infections have caused many fatalities around the world. There is an absence of a vaccine and an effective medication against these viruses. In this study, we analyzed the ability of dronabinol to act as a potential cure against these viral infections. We performed the docking of dronabinol with several viral proteins followed by molecular dynamics simulation, MM/PBSA and PCA analysis. We checked the ability of the polyphenol dronabinol to interfere with the binding of viral helicases to their cellular targets. We performed 2 D-QSAR studies, drug likeliness, ADMET and target prediction studies. From our study, we observed that dronabinol had the best docking ability against the helicase proteins of dengue and zika. Molecular dynamics simulation and MM/PBSA investigation confirmed the stability of the binding while PCA investigation showed a lowering of molecular motions in response to dronabinol docking to the helicases. Dronabinol interfered in the binding of the helicases to RNA. 2 D QSAR studies revealed a low IC50 value for dronabinol. Dronabinol showed favorable drug-likeness, ADMET properties and target prediction results. Thus we propose dronabinol be further investigated in-vitro as a cure against dengue and zika virus infections. Communicated by Ramaswamy H. Sarma