Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach

Frimayanti, Neni and Chee, Chin Fei and Zain, Sharifuddin Md and Abd Rahman, Noorsaadah (2011) Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach. International Journal of Molecular Sciences, 12 (2). pp. 1089-1100. ISSN 1422-0067, DOI

Full text not available from this repository.
Official URL:


Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A) and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA). The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy) were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA) with various substituents. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Department of Chemistry, Faculty of Science Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA
Uncontrolled Keywords: Binding energy, Complexation energy, Dengue NS2B/NS3 protease, Interaction energy, Molecular docking, 4 hydroxypanduratin a, antivirus agent, asparagine, histidine, nonstructural protein 2, nonstructural protein 2B, nonstructural protein 3, panduratin a, proteinase inhibitor, serine, unclassified drug, article, catalysis, complex formation, dengue, Dengue virus 2, drug design, drug structure, enzyme active site, enzyme activity, enzyme inhibition, hydrogen bond, hydrophilicity, hydrophobicity, nonhuman, serotype, Boesenbergia rotunda, Dengue virus
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Miss Malisa Diana
Date Deposited: 13 May 2013 01:17
Last Modified: 23 Dec 2019 04:05

Actions (login required)

View Item View Item