Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase

Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok 16424 Indonesia.
Bioinformation (Impact Factor: 0.5). 04/2012; 8(8):348-52. DOI: 10.6026/97320630008348
Source: PubMed


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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