Herbal Lead as Ideal Bioactive Compounds Against Probable Drug Targets of Ebola Virus in Comparison with Known Chemical Analogue: A Computational Drug Discovery Perspective

Abstract

Ebola is a deadly virus that has recently emerged as an enormous public health concern which causes dangerous illness with high fatality rates of 90 %. The virus is not receptive to known antivirals, and hence, there is a promising need to identify novel inhibitors to combat the disease. The present study deals with identification of potential herbal leads that probably subdue the activity of four major drug targets of Ebola virus such as VP24, VP30, VP35 and VP40 by computer-aided virtual screening. The selection of receptors was performed based on their functional roles in the disease. The drug likeliness and ADMET parameters of 150 herbal ligands were computationally predicted. Those molecules that qualified these parameters were preferred for docking studies with the protein targets. An existing chemical antiviral drug, BCX4430 was also docked and its theoretical binding energy was scrutinized. The docking studies suggested that herbal ligand Limonin demonstrated high binding properties with VP24 and VP35 (binding energy -9.7 kcal/mol). Similarly, curcumin exhibited good binding with VP30 (binding energy -9.6 kcal/mol). Further, Mahanine displayed superior interaction with VP40 (binding energy -7.7 kcal/mol). These herbal leads demonstrated better binding potential than the known chemical analogue in the computational studies. This study serves to bestow paramount information for further experimental studies concerning the utility of herbal ligands as probable lead molecules against Ebola viral targets.

Integrated Computational Approach for Virtual Hit Identification against Ebola Viral Proteins VP35 and VP40

“…Consequently, such compounds should be removed to prevent possible toxicity during early stages of drug development [61]. Limonin [62] and Neoglucobrassicin [63] were predicted as anti-Ebola compounds but showed high-risk structural alerts, including (a) high-risk epoxides that form protein adducts, thus potentially disturbing signal transduction cascades [64] and (b) high-risk quinones that lead to the formation of reactive oxygen species (ROS) and cause severe oxidative stress [65]. Furthermore, quinone-like compounds comprise structures that are widely reported to yield false positives or are inactive [60].…”

Insights into Ebola Virus VP35 and VP24 Interferon Inhibitory Functions and their Initial Exploitation as Drug Targets

“…Another docking study performed by Setlur et al suggested that herbal leads limonin ( Figure 5) and gummosin reported high predicted binding energy of -9.7 kcal/mol and -9.1 kcal/mol, respectively, for both VP35 (PDB ID: 4IJE) and VP24 (PDB ID: 4M0Q) [124]. In addition, samarcandin were reported to have high docked energy (-9.4 kcal/mol) in complex with VP24, while polyanthin (-9.0 kcal/mol) with VP35 (Setlur, Naik, and Skariyachan 2016).…”

Perspectives towards antiviral drug discovery against Ebola virus

“…However, the refinement of the model often does not meet the desired level of accuracy . A number of potential in silico studies have been documented over last few years which include homology modeling of unresolved EBOV polymerase and docking‐based virtual screening of compounds that have potential to bind with important residues lining the binding pocket of EBOV VP40, VP24, VP30, and VP35 …”