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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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
Microbiology Spectrum, Volume 10, No. 4, Year 2022
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Description
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. © 2022 Lubinski et al.
Authors & Co-Authors
Phan, My V.T.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Bugembe, Daniel Lule
United Kingdom, London
London School of Hygiene & Tropical Medicine
Cotten, Matt
United Kingdom, London
London School of Hygiene & Tropical Medicine
United Kingdom, Glasgow
Mrc-university of Glasgow Centre for Virus Research
Whittaker, Gary R.
United States, Ithaca
Cornell University
Statistics
Citations: 35
Authors: 4
Affiliations: 3
Identifiers
Doi:
10.1128/spectrum.01514-22
ISSN:
21650497
Research Areas
Cancer
Study Locations
Uganda