Malacitanolide, reissantin E and paclitaxel compounds as inhibitors of envelope, NS5 and NS2B/NS3 target proteins of dengue virus: Computational docking and molecular dynamics simulations studies

Abstract

ObjectiveThe objective of this study is to find out the role of terpenoid compounds as potential inhibitors against certain protein targets of dengue virus. MethodsThe 2-dimensional structures of terpenoid compounds were retrieved from the PubChem database. They were analysed for their interactions with target proteins of dengue virus such as envelope (1OKE), NS5 (1R6A-RPV & SHA) and NS2B/NS3 (4M9K) by docking studies followed by molecular dynamics (MD) simulations using Schrödinger software, version 10.7. ResultsOut of 513 terpenoid compounds studied, malacitanolide showed the highest interaction energy values of −7.072 kcal/mol (hydrogen bond (HB) interactions with Thr280, Gln200, Gln271, Gln49 and Ala50), −5.295 kcal/mol (HB interactions with Ser150, Lys29, Ser214) and −4.030 kcal/mol (HB interactions with Glu1169 and Asn1119) against 1OKE, 1R6A-RPV and 4M9K targets, respectively. Paclitaxel had shown the interaction energy value of −9.334 kcal/mol (HB with Lys61, Asp146, Trp87, Gly148, and Arg84) with 1R6A-SAH. MD simulation studies revealed that the best interacting compound malacitanolide maintained a stable complex with 1OKE of dengue virus. Malacitanolide, reissantin E, and paclitaxel exhibited very good interactions with all three-protein targets of dengue virus and had also shown significant stability. ConclusionsIn the present study, it is concluded that the terpenoid compounds malacitanolide, reissantin E, and paclitaxel could act as potential inhibitors against all three target proteins of dengue virus.