Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 123, Issue 5, Pages 935-946Publisher
WILEY
DOI: 10.1002/jcb.30237
Keywords
acridinedione analogs; capsid protein; dengue; MD simulations; molecular docking; umbrella sampling
Categories
Funding
- Department of Science and Technology, New Delhi, India [ECR/2016/000031]
- Board of Research in Nuclear Sciences, Department of Atomic Energy, Mumbai, India [37(1)/14/26/2015/BRNS]
- DBT, Government of India.
- Council of Scientific and Industrial Research, New Delhi
- Council of Scientific and Industrial Research of India
- CSIR [MLP:0201]
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This study discovered a compound that can efficiently bind to the DENV-2 C protein through virtual ligand screening. Molecular docking and dynamics simulations revealed strong interactions between the compound and DENV-2 C protein. The findings suggest that this compound could be a potential therapeutic molecule for treating dengue complications.
Dengue is a prominent viral disease transmitted by mosquitoes to humans that affects mainly tropical and subtropical countries worldwide. The global spread of dengue virus (DENV) is mainly occurred by Aedes aegypti and Aedes albopictus mosquitoes. The dengue virus serotypes-2 (DENV-2) is a widely prevalent serotype of DENV, that causes the hemorrhagic fever and bleeding in the mucosa, which can be fatal. In the life cycle of DENV-2, a structural capsid (DENV-2 C) protein forms the nucleocapsid assembly and bind to the viral progeny RNA. For DENV-2 maturation, the nucleocapsid is a vital component. We used virtual ligand screening to filter out the best in-house synthesized acridinedione analogs (DSPD molecules) that could efficiently bind to DENV-2 C protein. The molecular docking and dynamics simulations studies were performed to analyze the effect of DSPD molecules on DENV-2 C protein after binding. Our findings showed that DSPD molecules strongly interacted with DENV-2 C protein, as evident from molecular interactions and several time-dependent molecular dynamics-driven analyses. Moreover, this study was also supported by the thermodynamic binding free energy and steered molecular dynamics simulations. Therefore, we intend to suggest that the DSPD3 molecule could be used as a potential therapeutic molecule against dengue complications as compared to the cocrystallized inhibitor ST-148. However, further studies are required to demonstrate the ability of DSPD3 to induce DENV-2 C tetramer formation.
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