Identification and characterization of a non-biological small molecular mimic of a Zika virus conformational neutralizing epitope

ABSTRACT: Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput FACS_x0002_based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera. Deep sequencing of the DNA from the “Zika-only” beads identified 40 candidate molecular structures. A lead candidate small molecule “CZV1-1” was selected that correctly identifies serum specimens from Zika-experienced patients with good sensitivity and specificity (85.3% and 98.4%, respectively). Binding competition studies of purified anti-CZV1-1 IgG against known ZIKV-specific monoclonal antibodies showed that CZV1-1 mimics a nonlinear, neutralizing conformational epitope in the domain III of the ZIKV envelope. Purified anti-CZV1-1 IgG neutralized infection of ZIKV in cell cultures with potencies comparable to highly specific ZIKV_x0002_neutralizing monoclonal antibodies. This study demonstrates an innovative approach for discovery of synthetic non-natural molecular mimics of conformational virus epitopes. Such molecular mimics may have value in the development of novel diagnostic assays and vaccines for Zika, as well as for other viruses.

ORGANISM(S): synthetic construct

PROVIDER: GSE254062 | GEO | 2026/01/31

REPOSITORIES: GEO