ArticleMicrobiology spectrum2022
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.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 49 citations in OpenAlex.
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- Pathology and viral evolutionary dynamics in a hamster model of persistent SARS-CoV-2 infection.Communications biology · 2026Article
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- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Genetic diversity and spread dynamics of SARS-CoV-2 variants present in African populations.Royal Society open science · 2024Article
- Screening Peptide Drug Candidates To Neutralize Whole Viral Agents: A Case Study with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).ACS pharmacology & translational science · 2024Article
- High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1.Journal of virology · 2024Article
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- Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- A Noncoding A-to-U Kozak Site Change Related to the High Transmissibility of Alpha, Delta, and Omicron VOCs.Molecular biology and evolution · 2023Article
- Evolution of increased positive charge on the SARS-CoV-2 spike protein may be adaptation to human transmission.iScience · 2023Article
- SARS-CoV-2 variant biology: immune escape, transmission and fitness.Nature reviews. Microbiology · 2023Review
- SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works.International journal of molecular sciences · 2023Article
- Insight into SARS-CoV-2 Omicron variant immune escape possibility and variant independent potential therapeutic opportunities.Heliyon · 2023Review
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- SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression.PLoS biology · 2022Article
- Evolution of host protease interactions among SARS-CoV-2 variants of concern and related coronaviruses.bioRxiv : the preprint server for biology · 2022Article
- Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins.International journal of molecular sciences · 2022Article
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10 authors at 3 institutions in 3 countries.
Funding
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.
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