SARS-CoV-2 evolution enhances endocytic uptake while preserving TMPRSS2-dependent fusion.

ABSTRACT:

Background

Of the five SARS-CoV-2 variants-of-concern (VOC), Omicron shows increased transmissibility and infectivity, but lower pathogenicity. This drop in virulence was associated with an altered entry of VOC Omicron into airway epithelia by endocytosis instead of direct fusion, increasing virus replication in the upper airways and decreasing spread to the lower respiratory tract.

Methods

We aimed to assess the extent of direct fusion and endocytosis in nine clinical SARS-CoV-2 isolates collected during the SARS-CoV-2 pandemic, comprising wild-type (n=1), Alpha (n=2), Delta (n=1), and Omicron (n=5) strains. Viral entry was investigated in four different human cell lines in the presence of camostat, an inhibitor of TMPRSS2-mediated fusion, and aloxistatin, a cathepsin prote

SUBMITTER: Magnus CL 

PROVIDER: S-EPMC12832645 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature