Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach
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...
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| Format: | Article |
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2011
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| author | Frimayanti, Neni Chee, Chin Fei Zain, Sharifuddin Md Abd Rahman, Noorsaadah |
| author_facet | Frimayanti, Neni Chee, Chin Fei Zain, Sharifuddin Md Abd Rahman, Noorsaadah |
| author_sort | Frimayanti, Neni |
| collection | UM |
| description | 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. |
| first_indexed | 2024-03-06T05:15:50Z |
| format | Article |
| id | um.eprints-6055 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:15:50Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | um.eprints-60552019-12-23T04:05:03Z http://eprints.um.edu.my/6055/ Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach Frimayanti, Neni Chee, Chin Fei Zain, Sharifuddin Md Abd Rahman, Noorsaadah QD Chemistry 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. 2011 Article PeerReviewed 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 https://doi.org/10.3390/ijms12021089 <https://doi.org/10.3390/ijms12021089>. https://doi.org/10.3390/ijms12021089 10.3390/ijms12021089 |
| spellingShingle | QD Chemistry Frimayanti, Neni Chee, Chin Fei Zain, Sharifuddin Md Abd Rahman, Noorsaadah Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title | Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title_full | Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title_fullStr | Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title_full_unstemmed | Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title_short | Design of new competitive dengue Ns2b/Ns3 protease inhibitors-a computational approach |
| title_sort | design of new competitive dengue ns2b ns3 protease inhibitors a computational approach |
| topic | QD Chemistry |
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