The abstract is read at the publisher; the summary is JClub's.
Loss of phosphorylation at conserved spike residue Y674 (Y674F) ablates S1/S2 cleavage on virions and reduces TMPRSS2-dependent entry, especially in human airway cells.
- Why it matters: Spike processing efficiency and which host proteases are used are key determinants of SARS-CoV-2 infection and disease in airways, yet how specific S1/S2-loop modifications tune these steps is unclear.
- What they did: Mass spectrometry of purified virions from wild-type versus mutant SARS-CoV-2 identified phosphorylation at Y674, then reverse genetics created Y674F to remove phosphorylation capacity and tested replication and processing in Vero cells, a human respiratory cell line, and Golden Syrian hamsters.
- The result: Y674F replicated like wild-type in Vero cells but was attenuated in the human respiratory cell line; in hamsters it matched WT weight loss and lung viral titers yet showed reduced nasal viral load and diminished large-airway antigen staining, consistent with loss of S1/S2 cleavage and reduced TMPRSS2 utilization.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.