GP and NPC1 herbal targeted compounds in drug discovery and development a?? An in silico evidence for Ebola drugs

摘要

In silico based drug design is one of the most potential techniques in the discovery of new drug leads against essential drug targets. Ebola viruses (EBOV) of Filoviruses, consists of five species, viz. Zaire, Sudan, Ivory Coast, Bundibugyo, and Ravn, which acts by spreading hemorrhagic fatal fever worldwide. The reservoirs are yet to be confirmed, but the fruit bats have been considered to be the possible hosts for the serious transmissions. EBOV pathogenesis mainly depends on viral recognition, attachment and transmission of virion to host cell and lysis. Recent research reveals that apart from its own proteins (to be named, NP, VP35, VP40, glycoprotein (GP), sGP, VP30, VP24, and RNA-dependent RNA polymerase (L)), the EBOV use Niemann-Pick C1 for the transmission. In this study, a preliminary assessment of the natural compounds (Ayurvedic plants) are carried out based on bioavailability criteria, and were docked with potential drug targets of Ebola virus. Out of the seventeen leads, six (neoandrographalide, fumaric acid, vasicoline, andrographalide and andrograpanine) showed prominent binding sites of GPs and NPC1s proteins. These drugs bind to the residues responsible for native conformation of the viral proteins (GPs and NPC1s). Since, the natural compounds show minimal side-effects compared to the synthetic, the use of these compounds or formulations possessing them through a proper delivery platform or as leads for future drugs will upgrade the mode of ebola treatment.