Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract

Abstract

Background: The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and became the globally dominant variant by January 2022. Authentic virus and pseudovirus systems have shown Omicron spike has an increased dependence on the endosomal pathway for entry. Methods: We investigated the entry mechanisms of Omicron, Delta, and ancestral viruses in cell models that represent different parts of the human respiratory tract, including nasal epithelial cells (hNECs), large-airway epithelial cells (LAECs), small-airway epithelial cells, and embryonic stem cell-derived type II alveolar cells. Findings: Omicron had an early replication advantage in LAECs, while Delta grew to higher titers in all cells. ..