The SARS-CoV-2 envelope PDZ binding motif acts as a virulence factor disrupting host's epithelial cell-cell junctions.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), disrupts the alveolar epithelial barrier and exacerbates airway inflammation, leading to acute respiratory failure. The Envelope (E) protein is key to virulence, notably through its PDZ-binding motif (PBM), which interacts with host PDZ proteins, affecting signaling pathways and pathogenicity. This study investigates the PBM's role in virulence by generating PBM-deficient mutant viruses and assessing their impact in vitro and in vivo. The mutants showed delayed replication and reduced cytopathic effects in vitro. In vivo, infected hamsters exhibited less weight loss, lower viral loads, and reduced inflammation, indicating attenuated pathogenicity. Histological analysis confirm

SUBMITTER: Alvarez F 

PROVIDER: S-EPMC12255046 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature