HTRF-based identification of small molecules targeting SARS-CoV-2 E protein interaction with ZO-1 PDZ2.

ABSTRACT: The SARS-CoV-2 E protein through its C-terminal PDZ-binding motif (PBM) interacts with several host PDZ-containing proteins, including Zonula occludens-1 (ZO-1) protein via its PDZ2 domain, thereby contributing to viral pathogenesis. Targeting this interaction represents a potential therapeutic strategy. In this study, we determined the X-ray structure of the E PBM peptide in complex with the ZO-1 PDZ2 domain at 1.7 Å resolution. The structure revealed a domain-swapped dimer conformation of ZO-1 PDZ2, with the E PBM peptide conventionally bound within the PDZ domain's canonical binding groove, exhibiting key interactions characteristic of type II PBM/PDZ interactions. To identify potential inhibitors of the E PBM/ZO-1 PDZ2 interaction, we performed a Homogeneous Time-Resolved Fluorescence

SUBMITTER: Alvarez F 

PROVIDER: S-EPMC12808273 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature