PT  - JOURNAL ARTICLE
AU  - Bailey Lubinski
AU  - Tiffany Tang
AU  - Susan Daniel
AU  - Javier A. Jaimes
AU  - Gary R. Whittaker
TI  - Functional evaluation of proteolytic activation for the SARS-CoV-2 variant B.1.1.7: role of the P681H mutation
AID  - 10.1101/2021.04.06.438731
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.06.438731
4099  - http://biorxiv.org/content/early/2021/04/08/2021.04.06.438731.short
4100  - http://biorxiv.org/content/early/2021/04/08/2021.04.06.438731.full
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent behind the current COVID-19 pandemic having emerged in Wuhan China in late 2019 from a yet to be determined animal reservoir. SARS-CoV-2 B.1.1.7, a variant identified in the UK in late 2020, contains a higher than typical level of point mutants across its genome, including P681H in the spike S1/S2 cleavage site. Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from Wuhan-Hu1 and B.1.1.7 and observed no definitive difference in furin cleavage between Wuhan-Hu1 and B.1.1.7 in vitro. We performed functional assays using pseudo-typed particles harboring SARS-CoV-2 spike proteins and observed no significant differences between Wuhan-Hu1, Wuhan-Hu1 P681H or B.1.1.7 spike-carrying pseudo-typed particles in VeroE6 or Vero-TMPRSS2 cells, despite the spikes containing P681H being more efficiently cleaved. Likewise, we or show no differences in cell-cell fusion assays using the spike P681H-expressing cells. Our findings suggest that while the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC).Competing Interest StatementThe authors have declared no competing interest.