SCREENING OF COMPETITIVE INHIBITOR OF HEPARAN SULFATE IN JAPANESE ENCEPHALITIS
Abstract
ABSTRACT
Objective: Japanese encephalitis virus (JEV) causes central nervous system inflammatory disease Japanese encephalitis (JE), which is mainly caused
in children below 15 years of age. On an estimate, there are around 3 billion people at the risk and the disease is continuously spreading globally. The
JEV belongs to Flavivirdiae family and has RNA genome. JEV envelope protein domain III (D-III) binds to the Heparan sulfate present on the cell surface
and initiates the infection which causes the disease in children.
Methods: The drug discovery and development process has become more quantitative and much more computational in recent years. In this study,
comparative molecular docking studies of 200 zinc database compounds and Heparan sulfate were done with D-III of JEV using Autodock 4.2 and the
results were analyzed on the basis of binding energy, inhibition constant, and number of hydrogen bonds. The results were also analyzed by studying
the absorption, distribution, metabolism, and excretion (ADME-T) properties of the compounds using admetSAR server.
Results: Best three lead molecules zinc_8964844 zinc_8964845, zinc_12660861 were chosen based on the binding energy, inhibition constant and
ADME properties among a set of 200 ligands that can act as the competitive inhibitor of the Heparan sulfate, which presents on the surface of the host
cell and mediates the attachment and binding of the virus to the host cell.
Conclusion: These compounds can act as the competitive inhibitor of the Heparan sulfate and they can be validated further as a drug for the treatment of JE.
Keywords: Japanese encephalitis, Domain-III, Heparan sulfate, Autodock, Autodock, Absorption, Distribution, Metabolism, Excretion.
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