PT  - JOURNAL ARTICLE
AU  - Bailey Lubinski
AU  - Maureen H. V. Fernandes
AU  - Laura Frazier
AU  - Tiffany Tang
AU  - Susan Daniel
AU  - Diego G. Diel
AU  - Javier A. Jaimes
AU  - Gary R. Whittaker
TI  - Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike
AID  - 10.1101/2021.04.06.438731
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.06.438731
4099  - http://biorxiv.org/content/early/2021/11/01/2021.04.06.438731.short
4100  - http://biorxiv.org/content/early/2021/11/01/2021.04.06.438731.full
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the COVID-19 pandemic. SARS-CoV-2 B.1.1.7 (Alpha), a WHO variant of concern (VOC) first identified in the UK in late 2020, contains several mutations including P681H in the spike S1/S2 cleavage site, which is predicted to increase cleavage by furin, potentially impacting the viral cell entry. Here, we studied the role of the P681H mutation in B.1.1.7 cell entry. We performed assays using fluorogenic peptides mimicking the Wuhan-Hu-1 and B.1.1.7 S1/S2 sequence and observed no significant difference in furin cleavage. Functional assays using pseudoparticles harboring SARS-CoV-2 spikes and cell-to-cell fusion assays demonstrated no differences between Wuhan-Hu-1, B.1.1.7 or a P681H point mutant. Likewise, we observed no differences in viral growth between USA-WA1/2020 and a B.1.1.7 isolate in cell culture. Our findings suggest that while the B.1.1.7 P681H mutation may slightly increase S1/S2 cleavage this does not significantly impact viral entry or cell-cell spread.HighlightsSARS-CoV-2 B.1.1.7 VOC has a P681H mutation in the spike that is predicted to enhance viral infectionP681H does not significantly impact furin cleavage, viral entry or cell-cell spreadOther mutations in the SARS-CoV-2 B.1.1.7 VOC may account for increased infection ratesCompeting Interest StatementThe authors have declared no competing interest.