Molecular Docking of Traditional Chinese Medicinal Compounds Against Dengue Virus NS3 Protease and NS3 Helicase

Dengue virus (DENV) NS3 protease and NS3 helicase are important in polyprotein processing and viral replication. Thus, these enzymes make promising targets for designing lead molecules against DENV. Amino acid sequences of NS3 protease and helicase molecules from Philippine and non-Philippine strains of DENV were aligned to determine their degree of conservation and structural homology. The Philippine strains with the highest sequence identity with their PDB template were selected for homology modeling. A total of 6,699 curated molecules from the Traditional Chinese Medicines Systems Pharmacology (TCMSP) database were docked to the NS3 protease and helicase models using Autodock Vina. The top three binding ligands (MOL003959, MOL004226 and MOL008458) with high solubility, and Lipinski's rules values within the suitable range were recommended for optimization. These may be suitable candidates for drug lead development against the protease (DENV2 Kawashima & Shihada) and helicase (DENV4 Henn & Yip) Philippine strains of DENV.