Develop dengue and zika virus inhibitors : simulation of small drug molecules with e-protein dimer

Abstract

Dengue and Zika have been pestering 40% of human population since ancient time until now, yet human still struggling to come up with a solution against them. Due to the advancement of technology, not only there are sufficient approved drugs in the market available for drug repurposing, the effort to find a cure gainst Dengue and Zike virus can be further reduced by in silico screening. A novel binding pocket in virus envelope protein, β-oG could inhibit viral infection when blocked. This pocket was docked against around 2,000 approved drugs by Mr. Abhishek Kurma, and Itraconazole was identified as high affinity binder to β-oG pocket. In this project, simulation of Itraconazole in E-protein was run for all serotypes and Zika. Next, trajectory, root mean square deciation, solvent accessible surface area, hydrogen bonds, number of contacts and neighbouring residues were calculated and analysed. In overall, Itraconazole is very stable in Dengue 2, 4 and Zika E-protein. The binding is weaker in Dengue 3 E-protein and appeared weakest in Dengue 1 E-protein. Further analysis on different drug molecules in E-protein may be needed to validate the result. The drug was preparing to be tested on cell culture.