ArticleScience advances2022
The D614G mutation redirects SARS-CoV-2 spike to lysosomes and suppresses deleterious traits of the furin cleavage site insertion mutation.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- BST-2 inhibits SARS-CoV-2 egress at intracellular membranes and is neutralized by ORF7a.Scientific reports · 2026Article
- D614G reshapes allosteric networks and opening mechanisms of SARS-CoV-2 spikes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Droplet-based single-cell pairing for high-throughput interaction mapping of antigen-receptor combinations.Science advances · 2025Article
- SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.PLoS pathogens · 2025Article
- Nonlytic Egress and Transmission in the Virus World.Annual review of biochemistry · 2025Review
- The Role of Long-Range Non-Specific Electrostatic Interactions in Inhibiting the Pre-Fusion Proteolytic Processing of the SARS-CoV-2 S Glycoprotein by Heparin.Biomolecules · 2025Article
- Therapeutic application of extracellular vesicles in human diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants.The EMBO journal · 2024Article
- Application of machine learning algorithms to identify serological predictors of COVID-19 severity and outcomes.Communications medicine · 2024Article
- Article
- Review
- Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein.bioRxiv : the preprint server for biology · 2024Article
- Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes.Research square · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress occurs by lysosomal exocytosis. We show that the Spike D614G mutation enhances Spike trafficking to lysosomes, drives Spike-mediated reprogramming of lysosomes, and reduces cell surface Spike expression by ~3-fold. D614G is not a human-specific adaptation. Rather, it is an adaptation to the earlier furin cleavage site insertion (FCSI) mutation that occurred at the genesis of SARS-CoV-2. While advantageous to the virus, furin cleavage of spike has deleterious effects on spike structure and function, inhibiting its trafficking to lysosomes and impairing its infectivity by the transmembrane serine protease 2(TMPRSS2)-independent, endolysosomal pathway. D614G restores spike trafficking to lysosomes and enhances the earliest events in SARS-CoV-2 infectivity, while spike mutations that restore SARS-CoV-2's TMPRSS2-independent infectivity restore spike's trafficking to lysosomes. Together, these and other results show that D614G is an intragenic suppressor of deleterious traits linked to the FCSI and lend additional support to the endolysosomal model of SARS-CoV-2 egress and entry.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.