Identification and structural characterization of small molecule fragments targeting Zika virus NS2B-NS3 protease

In this study, we screened a fragment compound library against the Zika protease using a primary thermal shift assay and identified twenty-two fragments which (bind to and) stabilize the protease. We then determined the X-ray crystal structures of two hits from different classes, all of which bind to the S1 pocket next to the protease active site. We confirmed that these two fragments bind to the protease without inducing significant conformational changes using solution NMR spectroscopy. These fragment scaffolds serve as the starting point for subsequent lead compound development.

Source: Antiviral Therapy - January 15, 2020 Category: Virology Source Type: research