Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

Characterization of the enzymatic inhibition-Previously, a small molecule p-Nitrophenyl-pguanidino benzoate (Fig. 3D ) has been identified to specifically bind to the active site of West Nile NS2B-NS3pro by molecular dynamics (MD) simulations, followed by NMR binding confirmation (19) . Later, this molecule has been extensively demonstrated to bind Dengue (Table 1 ). Most strikingly, as clearly evidenced from Lineweaver-Burk plots for both linked (Fig. 3E ) and unlinked (Fig. 3G ) Zika complexes, the small molecule acts as a non-competitive inhibitor for both forms. We have searched all literatures citing the original paper (19) , but only found IC50 value of this inhibitor on West Nile NS2B-NS3pro complex (34.2 µM) in the original paper (19) . Therefore, this inhibitor could inhibit the enzymatic activity of Zika NS2B-NS3pro much more potently than that of author/funder. All rights reserved. No reuse allowed without permission.