TY - JOUR
AU - Lubinski, Bailey
AU - Frazier, Laura E.
AU - Phan, My V.T.
AU - Bugembe, Daniel L.
AU - Cunningham, Jessie L.
AU - Tang, Tiffany
AU - Daniel, Susan
AU - Cotten, Matthew
AU - Jaimes, Javier A.
AU - Whittaker, Gary R.
PY - 2022
DA - June
TI - 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
JO - Microbiology Spectrum
DO - http://dx.doi.org/10.1128/spectrum.01514-22
AB - 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.
PB - American Society for Microbiology
UR - http://eprints.gla.ac.uk/274617/
KW - Coronavirus (COVID-19)
ER