The NS3 helicase plays a significant role in the Zika virus life cycle, cataylizing the unwinding of virus double stranded RNA into single strands prior to replication. Given its vital role in the virus life cycle, NS3 is a potential target for drug design. This investigation focuses on studying the conformational dynamics of the Zika virus NS3 helicase protein for the purposes of allosteric drug design. Using simulations of apo (inactive) and the ssRNA-bound (active) forms, our results provide key information on the structural differences between both states. With drug docking and virtual screening software packages, we have detected a few potential allosteric sites and have generated a list of viable drugs. To further confirm the viability of the investigated compounds as inhibitors, we ran simulations of the protein-drug complexes for the top 10 highest scoring docked drugs at each predicted site. Structural changes in the P-loop (the RNA binding loop) and in the residues at the ATP hydrolysis site due the binding of different drug candidates are determined. A considerable shift in the structural and dynamic behavior of these regions will be the preliminary indication of potential allosteric inhibition. The compounds inducing this behavior will then be considered candidates for future optimizations.

Allosteric inhibition of the Zika virus NS3 helicase

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.