Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract
Date
2023
Authors
Gartner, M.J.
Lee, L.Y.Y.
Mordant, F.L.
Suryadinata, R.
Chen, J.
Robinson, P.
Polo, J.M.
Subbarao, K.
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Journal article
Citation
Med, 2023; 4(12):944-955.e7
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Matthew J. Gartner, Leo Yi Yang Lee, Francesca L. Mordant, Randy Suryadinata, Joseph Chen, Philip Robinson, Jose M. Polo, Kanta Subbarao
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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. Omicron maintained dependence on serine proteases for entry in all culture systems. While serine protease inhibition with camostat was less robust for Omicron in hNECs, endosomal entry was not enhanced. Conclusions Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract.
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Crown Copyright © 2023 Published by Elsevier Inc.