Title: Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors
Authors: Jadav, Surender Singh ×
Kaptein, Suzanne
Timiri, Ajaykumar
De Burghgraeve, Tine
Badavath, Vishnu Nayak
Ganesan, Ramesh
Sinha, Barij Nayan
Neyts, Johan
Leyssen, Pieter
Jayaprakash, Venkatesan #
Issue Date: Apr-2015
Publisher: Pergamon Press
Series Title: Bioorganic & Medicinal Chemistry Letters vol:25 issue:8 pages:1747-52
Article number: 10.1016/j.bmcl.2015.02.059
Abstract: The β-OG pocket is a cavity in the flavivirus envelope (E) protein that was identified by Proc. Natl. Acad. Sci. U.S.A.2003, 100, 6986 as a promising site for the design of antiviral agents that interfere with virus entry into the host cell. The availability of the X-ray crystal structure of the dengue virus (DENV) E protein provided an opportunity for in silico drug design efforts to identify candidate inhibitors. The present study was set up to explore whether it is possible to generate a novel class of molecules that are hybrids between two hit compounds that have been reported previously by ACS. Chem. Biol.2008, 3, 765 following an in silico screening effort against the DENV E protein. First, a library of twenty hybrid molecules were designed and synthesized to explore the feasibility of this strategy. Antiviral evaluation in a virus-cell-based assay for DENV proved this approach to be successful, after which another twenty-four molecules were produced to further explore and optimize the potency of this novel class of hybrid inhibitors. In the end, a molecule was obtained with an EC50 against dengue virus serotype 2 in the low micromolar range (23, 1.32±0.41μM).
ISSN: 0960-894X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Academic Center for General Practice
× corresponding author
# (joint) last author

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