In silico studies on Zika NS3 helicase: bedrock for antiviral drug design
Abstract
Zika virus is a re-emerging infectious disease, which was declared to be a public health emergency of international concern due to its various reported complications ranging from microcephaly in newborn to Guillain-Barré Syndrome (GBS). Because less attention has been paid to this virus over time, literature has been lacking regarding the structural and conformational features of its proteins particularly the NS3 helicase protein. This dissertation has addressed two major aspects of Zika NS3 helicase protein: (i) the binding interactions and (ii) structural dynamics and conformational changes of the protein. Investigations were carried out on the various Zika NS3 helicase ligand binding landscapes using 10 ligands via molecular docking, of which the best 3 were subjected to molecular dynamic simulations and several post dynamics analyses. Ivermectin, HMC-HO1α and lapachol emerged as the best 3 ligands. The result of the analysis showed that the binding of Ivermectin to ssRNA site and Lapachol and HMC-HO1α to the ATPase site induces a more compact protein structure, thus stabilizing residue fluctuations. The pharmacophoric characteristics found in Lapachol, HMC-HO1α and Ivermectin may be utilized in the design of a potent hybrid drug that can show efficient inhibition of a multitude of diseases including the detrimental co-infection of ZIKV, Dengue and Chikungunya. Also in this study, a detailed structural dynamic analysis was carried out on the structural flexibility of the…
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Evidence Hub reads this as a thesis, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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