e-ISSN 2231-8542
ISSN 1511-3701
Suriyea Tanbin, Nurhainis Ogu Salim and Fazia Adyani Ahmad Fuad
Pertanika Journal of Tropical Agricultural Science, Volume 27, Issue 4, October 2019
Keywords: 2-deoxyglucose, alpha-D-glucose, beta-D-glucose-6-phosphate, Human Hexokinase II (HK2), ligand-based screening, structure-based screening, toxicity test
Published on: 21 October 2019
The human hexokinase isoform II (HKII) is one of the important enzymes for dengue virus (DENV) replication and thus has been suggested as a potential therapeutic target for DENV drug development. In this work, compounds were identified using Ultrafast Shape Recognition with CREDO Atom Types (USRCAT) by utilizing both HKIIs substrate and product; alpha-D-glucose (GLC) and beta-D-glucose-6-phosphate (BG6), as well as a known HKIIs inhibitor, 2-deoxyglucose (2DG), as the query molecules. The analogues of the three query molecules were subsequently docked against the HKIIs crystal structure (PDB ID: 2NZT) by using Auto Dock 4 program on Chain B, where the active sites and strong bonds were located. Among the top-ranked compounds, Compound 4 (ZINC26898487), which was the most similar to 2DG, showed the best binding energy (-7.63 kcal/mol) and contained two H bonds. Compound 9 (ZINC16930948), an analogue of GLC emerged as the best inhibitor candidate because it had six H bonds. Similarly, among the molecules similar to BG6, Compound 14 (ZINC4403351) had been suggested as a potential inhibitor because it contained four strong H bonds. All compounds were predicted to be non-toxic, based on Toxicity Estimation Software Tool (TEST) analysis. By providing these valuable findings, this study has paved the way for the discovery of compounds that should be further tested for the development of anti-dengue drugs.
ISSN 1511-3701
e-ISSN 2231-8542