Title |
Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase |
Authors |
Syarifuddin Idrus, Usman Sumo Friend Tambunan* & Ahmad Ardilla Zubaidi |
Affiliation |
Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok 16424 Indonesia.
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usman@ui.ac.id; *Corresponding author
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Article Type |
Hypothesis
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Date |
Received April 11, 2012; Accepted April 16, 2012; Published April 30, 2012
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Abstract |
NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.
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Keywords |
Dengue virus, cyclopentapeptide, NS5 methyltransferase, antiviral drug, inhibitor.
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Citation |
Idrus et al.
Bioinformation 8(8): 348-352 (2012) |
Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |