Identification of Novel Target Sites and an Inhibitor of the Dengue Virus E Protein

Overview

Journal J Comput Aided Mol Des

Publisher Springer

Specialties Biomedical Engineering
Molecular Biology

Date 2009 Feb 26

PMID 19241120

Citations 25

Authors

Ragothaman Yennamalli

Naidu Subbarao

Thorsten Kampmann

Ross P McGeary

Paul R Young

Bostjan Kobe

Affiliations

Soon will be listed here.

Abstract

Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC(50) in the micromolar range against dengue virus type 2.

Citing Articles

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Small-Molecule Inhibition of Viral Fusion Glycoproteins.

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Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins.

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Identification of Zika Virus Inhibitors Using Homology Modeling and Similarity-Based Screening to Target Glycoprotein E.

Telehany S, Humby M, McGee Jr T, Riley S, Jacobs A, Rizzo R Biochemistry. 2020; 59(39):3709-3724.

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Target Identification Using Homopharma and Network-Based Methods for Predicting Compounds Against Dengue Virus-Infected Cells.

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