Mutation and docking studies on NS2b-NS3 complex from yellow fever virus towards drug discovery |
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Authors: | Prabhavathy Kannappan SundaraBaalaji Narayanan |
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Institution: | Structural Biology Lab, Department of Bioinformatics, School of Life Sciences, Bharathiar University, Coimbatore − 641046, India |
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Abstract: | Yellow fever virus is the causative agent of Yellow fever. The genome of the virus contains three structural and seven non-structural proteins. Of these seven nonstructural
proteins, NS2B-NS3 protein complex has protease activity required for viral replication. Predicting the 3D structure of this complex and studying the
interaction of residues at the recognized catalytic triad of the complex is an integral part to understand the virus replication mechanism. In the present study, the
structure was determined for NS2B-NS3 complex by Homology modeling and modeled structure was validated for its stability. Mutation studies at the residues
His94, Asp118 and Ser176 revealed that Asp118-His94 bond played an important role in the structural stability of NS2B-NS3 complex. This indicates site-directed
mutagenesis, controlling YFV replication, as one mechanism to design vaccine strains. Docking studies of the bioactive compounds at the active site of NS2B-NS3
complex also indicated 4-hydroxypanduratin A as potential lead compound for drug development. The theoretical models will further pave way to experimentally
verify our mutation and docking studies, thus taking a lead in pharmacogenomics and drug development.AbbreviationsYFV - Yellow Fever Virus,
WNV - West Nile Virus,
H-bonds - hydrogen bonds,
SNP - Single nucleotide polymorphism. |
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Keywords: | site-directed mutagenesis docking NS2B-NS3 complex |
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