The discovery of Zika virus NS2B-NS3 inhibitors with antiviral activity via an integrated virtual screening approach

• DOI: 10.1016/j.ejps.2022.106220
• Publication Date: 2022-05-24T00:59:14Z
• Authors: Muhammad Usman Mirza; Ida Alanko; Michiel Vanmeert; Kendall M. Muzzar...; Outi M.H. Salo-Ahen; Iskandar Abdullah; Iulia A. Kovari; Sandra Claes; Steven De Jonghe; Dominique Schols; Raymond F. Schinazi; Ladislau C. Kovari; John F. Trant; Sarfraz Ahmad; Matheus Froeyen
• Keywords: Zika Virus; NS3; Antiviral drug

With expanding recent outbreaks and a lack of treatment options, the Zika virus (ZIKV) poses severe health concern. The availability ZIKV NS2B-NS3 co-crystallized structures paved way for rational drug discovery. A computer-aided structure-based approach was used to screen diverse library compounds against protease. top hits were selected based on various binding free energy calculations followed by per-residue decomposition analysis. then evaluated their biological potential with protease inhibition assay antiviral activity. Among 26 compounds, 8 showed promising activity percentage greater than 25 3 displayed ∼50% at 10 µM, which indicates an enrichment rate approximately 36% (threshold IC50 < µM) in ZIKV-NS2B-NS3 assay. Of these, only one compound (23) produced whole-cell anti-ZIKV activity, mode 23 extensively analyzed through long-run molecular dynamics simulations. current study provides starting point further development novel ZIKV.