Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.

ABSTRACT: When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease an

SUBMITTER: Abrams RPM 

PROVIDER: S-EPMC7733812 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature