ArticleProceedings of the National Academy of Sciences of the United States of America2022
SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- VPS26A retromer complex and SNX27 mediate stress-induced Golgi bypass of membrane proteins.Nature communications · 2026Article
- Amphotericin B promotes respiratory viral entry by enhancing late endosomal maturation and fusion via glucocerebrosidase-mediated ceramide remodeling.Nature communications · 2026Article
- Identification of Cathepsin L as the Molecular Target of Hydroxychloroquine With Chemical Proteomics.Molecular & cellular proteomics : MCP · 2025Article
- Identification and targeting of regulators of SARS-CoV-2-host interactions in the airway epithelium.Science advances · 2025Article
- Sequences in the Cytoplasmic Tail Contribute to the Intracellular Trafficking and the Cell Surface Localization of SARS-CoV-2 Spike Protein.Biomolecules · 2025Review
- FishJournal of virology · 2024Article
- Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine.The EMBO journal · 2024Article
- Review
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response.Virologica Sinica · 2024Article
- Article
- Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy.Pharmacological reports : PR · 2024Review
- SNX32 is a host restriction factor that degrades African swine fever virus CP204L via the RAB1B-dependent autophagy pathway.Journal of virology · 2024Article
- Emerging Role of Sorting Nexin 17 in Human Health and Disease.Current protein & peptide science · 2024Review
- SNX27:Retromer:ESCPE-1-mediated early endosomal tubulation impacts cytomegalovirus replication.Frontiers in cellular and infection microbiology · 2024Article
- SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2023Article
- The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry.Viruses · 2023Article
- Plasma proteome dynamics of COVID-19 severity learnt by a graph convolutional network of multi-scale topology.Life science alliance · 2023Article
- Autophagy and SARS-CoV-2-Old Players in New Games.International journal of molecular sciences · 2023Review
- Autophagy in Inflammatory Response against SARS-CoV-2.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After binding to its cell surface receptor angiotensin converting enzyme 2 (ACE2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell through directly fusing with plasma membrane (cell surface pathway) or undergoing endocytosis traveling to lysosome/late endosome for membrane fusion (endocytic pathway). However, the endocytic entry regulation by host cell remains elusive. Recent studies show ACE2 possesses a type I PDZ binding motif (PBM) through which it could interact with a PDZ domain-containing protein such as sorting nexin 27 (SNX27). In this study, we determined the ACE2-PBM/SNX27-PDZ complex structure, and, through a series of functional analyses, we found SNX27 plays an important role in regulating the homeostasis of ACE2 receptor. More importantly, we demonstrated SNX27, together with retromer complex (the core component of the endosomal protein sorting machinery), prevents ACE2/virus complex from entering lysosome/late endosome, resulting in decreased viral entry in cells where the endocytic pathway dominates. The ACE2/virus retrieval mediated by SNX27-retromer could be considered as a countermeasure against invasion of ACE2 receptor-using SARS coronaviruses.
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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.