Background: Dengue fever, a major public health problem in the tropical and sub-tropical
countries caused by the infection of Dengue virus transmitted by the anthropod vectors. The dengue virus
infection is represented as the “Neglected Tropical Diseases” by the world health organization. The
structural protein E binds to the receptor on the host cell surface during infection and the binding directs
to the endocytic pathway. The conformational change of the envelope protein helps to infuse the viral
lipid membrane and delivers the viral genome into the cytosol. No specific treatments are available till
date and development of the vaccine for the DENV is challenging due to the immunization and longlasting
protection against all four serotypes. Hence, identification of potent inhibitors would overlay the
therapeutics against the mediated diseases.
Objective: Our study focuses on developing the novel potent inhibitors to inhibit the viral attachment
and membrane fusion of the Dengue virus Envelope protein.
Methods: The crystal structure of Dengue Envelope protein has been retrieved from the protein data
bank and optimized through Schrödinger. The structure-based virtual screening based on the cocrystallised
ligand has been carried out with the small molecule libraries, and based on the docking
score, interaction and energy value best complexes were selected. The selected complexes were further
taken forward for the conformational stability analysis through Molecular dynamics simulation.
Results: Around 55 molecules from the three databases were identified as potential binders to the envelope
protein and the docking studies revealed that the top compounds possess strong interaction with the
good energies. The Molecular electrostatic surface potential of the top five compounds states that the
interactions were observed mostly in the electropositive region. Finally, the best 5 compounds carried
further for molecular dynamics simulations exposed that they were highly stable and no loss of interactions
was observed between those complexes.
Conclusion: Hence, from the results, it is evident that the compounds DB00179, Quercetin, Silymarin,
Dapagliflozlin and Fisetin could be novel and potent candidates to inhibit the DENV envelope protein.