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

Objective: The objective of this study is to find out the role of terpenoid compounds as potential inhibitors against certain protein targets of dengue virus. Methods: The 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. Results: Out 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. Conclusions: In 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.