@article{Lubinski_B-2022_89347,
title = {Spike protein cleavage-activation in the context of the SARS-CoV-2 P681R mutation: an analysis from its first appearance in lineage A.23.1 identified in Uganda},
author = {Lubinski, B. and Frazier, L. and Phan, M. and Bugembe, D. and Cunningham, J. and Tang, T. and Daniel, S. and Cotten, M. and Jaimes, J. and Whittaker, G.},
month = {jun},
year = {2022},
abstract = {Based on its predicted ability to affect transmissibility and pathogenesis, surveillance studies have highlighted the role of a specific mutation (P681R) in the S1/S2 furin cleavage site of the SARS-CoV-2 spike protein. Here we analyzed A.23.1, first identified in Uganda, as a P681R-containing virus several months prior to the emergence of B.1.617.2 (Delta variant). We performed assays using peptides mimicking the S1/S2 from A.23.1 and B.1.617 and observed significantly increased cleavability with furin compared to both an original B lineage (Wuhan-Hu1) and B.1.1.7 (Alpha variant). We also performed cell–cell fusion and functional infectivity assays using pseudotyped particles and observed an increase in activity for A.23.1 compared to an original B lineage spike. However, these changes in activity were not reproduced in the B lineage spike bearing only the P681R substitution. Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R substitution, this substitution needs to occur on the background of other spike protein changes to enable its functional consequences.},
journal = {Microbiology Spectrum},
publisher = {American Society for Microbiology},
url = {http://dx.doi.org/10.1128/spectrum.01514-22},
}
