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Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1621335


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.

Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Endosomes/metabolism , SARS-CoV-2 , Sorting Nexins/chemistry , COVID-19/virology , Cell Line , Cell Line, Tumor , Cell Membrane/metabolism , Crystallography, X-Ray , Cytosol/metabolism , Endocytosis , Gene Expression Profiling , HEK293 Cells , HeLa Cells , Homeostasis , Humans , Lentivirus , Lysosomes/metabolism , Peptides/chemistry , Protein Binding , Protein Conformation , Protein Domains , Sorting Nexins/metabolism , Virus Internalization
Int J Environ Res Public Health ; 18(24)2021 12 08.
Article in English | MEDLINE | ID: covidwho-1593482


BACKGROUND: As the effectiveness on stress urinary incontinence (SUI) prevention of pelvic floor muscle training (PFMT) for pregnant women has been inconclusive, we are planning to conduct a trial to evaluate a video program designed for prevention of SUI developed through combining PFMT with global postural reeducation (GPR). METHODS: As a randomized controlled trial, eligible participants will be randomized (1:1) into an exercise group and a control group to perform PFMT regularly following video guidance or with no intervention, respectively. The experimental stage will be from the 16th gestation week (GW) to the 12th month postpartum, with eight appointments at the 16th, 28th, 37th GW, delivery, the 6th week and the 3rd, 6th, and 12th month postpartum. Data will be collected regarding urinary leakage symptoms, the stress test, the modified Oxford Scale, pelvic floor ultrasound, perineal laceration classification at delivery, neonatal Apgar score, and questionnaires (PISQ-12, ICIQ-UI SF, I-QOL, OABSS). The primary outcome is the occurrence of the symptomatic SUI and positive stress test at the 6th week postpartum. DISCUSSION: This protocol is anticipated to evaluate the efficacy of the intervention via video app for the design of a future randomized control trial (RCT). TRIAL REGISTRATION: The trial has been registered at Chinese Clinical Trial Registry (registration number: ChiCTR2000029618).

Mobile Applications , Urinary Incontinence, Stress , Exercise Therapy , Female , Humans , Multicenter Studies as Topic , Pelvic Floor , Pregnancy , Randomized Controlled Trials as Topic , Treatment Outcome , Urinary Incontinence, Stress/prevention & control