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

Syarifuddin Idrus,Usman Tambunan,Ahmad Ardilla Zubaidi

doi:10.6026/97320630008348

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.

Highlights

Dengue fever is a serious threat to global health issues
The backbond of Ser150 was performed hydrogen bonds with amine site of cystein and the Conclusion: We have performed several cyclic peptides as potential inhibitor of dengue virus NS5 Mtase through virtual screening using docking-based methods. These peptides were predicted to bind by forming hydrogen bonds to SAM and RNA-cap sites with higher binding free energy (∆Gbinding) than standards
CTWYC cyclic peptide is the best inhibitor of the SAM site with binding free energy (∆Gbinding) of -30.72 kcal/mol

Summary

Introduction

Dengue fever is a serious threat to global health issues. Geographic distribution of this disease has undergone tremendous expansion over the last 30 years. 100 countries are endemic for dengue fever and 40% of the world's population or about 2.5 billion people in the tropical and sub-tropics have an increased risk of catching the disease. The classification is based on the type of antibodies produced in the human body after infection. These four serotypes had the same morphology and genome but show different antigens so that a person can be infected with this virus more than once in the absence of complete crossprotection [2]

Methods

Findings

Conclusion