Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: March 27, 2020

Abstract Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV 2012, and the newly emerged SARS-CoV-2 late 2019. However, little is currently known about biology of SARS-CoV-2. Here, using S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) receptor for SARS-CoV-2, find enters 293/hACE2 cells mainly through endocytosis, PIKfyve, TPC2, cathepsin L are critical entry, less stable than S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry but not pseudovirions. Further studies recovered SARS COVID-19 patients’ sera show limited cross-neutralization, suggesting recovery from one infection might protect against other. Our results present potential targets development drugs vaccines

Language: Английский

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Lysosomes as dynamic regulators of cell and organismal homeostasis

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 101 - 118

Published: Nov. 25, 2019

Language: Английский

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Life in the lumen: The multivesicular endosome

Traffic, Journal Year: 2019, Volume and Issue: 21(1), P. 76 - 93

Published: Nov. 5, 2019

The late endosomes/endo-lysosomes of vertebrates contain an atypical phospholipid, lysobisphosphatidic acid (LBPA) (also termed bis[monoacylglycero]phosphate [BMP]), which is not detected elsewhere in the cell. LBPA abundant membrane system present lumen this compartment, including intralumenal vesicles (ILVs). In review, current knowledge on and LBPA-containing membranes will be summarized, their role control endosomal cholesterol outlined. Some speculations also made how may overwhelmed storage disorder Niemann-Pick C. Then, roles endo-lysosomal dynamics functions discussed broader terms. Likewise, mechanisms that drive biogenesis membranes, ESCRTs, discussed, as well diverse composition fate, degradation lysosomes secretion exosomes. This review discuss are hijacked by pathogenic agents during intoxication infection, what biochemical function intra-endosomal lumenal milieu. Finally, allude to size limitations imposed vesicle speculate possible calcium chelator acidic stores endo-lysosomes.

Language: Английский

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Ca2+ Fluxes and Cancer

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(6), P. 1055 - 1069

Published: June 1, 2020

Language: Английский

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Enzymatic Noncovalent Synthesis

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(18), P. 9994 - 10078

Published: Aug. 19, 2020

Enzymatic reactions and noncovalent (i.e., supramolecular) interactions are two fundamental nongenetic attributes of life. synthesis (ENS) refers to a process where enzymatic control intermolecular for spatial organization higher-order molecular assemblies that exhibit emergent properties functions. Like covalent (ECS), in which an enzyme catalyzes the formation bonds generate individual molecules, ENS is unifying theme understanding functions, morphologies, locations ensembles cellular environments. This review intends provide summary works within past decade emphasize After comparing ECS ENS, we describe few representative examples nature uses as rule life, create biomacromolecules properties/functions myriad processes. Then, focus on man-made (synthetic) molecules cell-free conditions, classified by types enzymes. that, introduce exploration context cells discussing intercellular, peri/intracellular, subcellular cell morphogenesis, imaging, cancer therapy, other applications. Finally, perspective promises developing assemblies/processes aims be updated introduction researchers who interested exploring science technologies address societal needs.

Language: Английский

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Parkinson’s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes

Cell, Journal Year: 2022, Volume and Issue: 185(13), P. 2292 - 2308.e20

Published: June 1, 2022

Language: Английский

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Targeting lysosomes in human disease: from basic research to clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 8, 2021

Abstract In recent years, accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis. Lysosomal changes dysfunction have been correlated with development numerous diseases. this review, we interpreted key biological functions four areas: metabolism, cell proliferation differentiation, immunity, death. More importantly, actively sought to determine characteristic cells affected by these diseases, causes dysfunction, their significance treatment human disease. Furthermore, outlined currently available targeting strategies: (1) lysosomal acidification; (2) cathepsins; (3) membrane permeability integrity; (4) calcium signaling; (5) mTOR (6) emerging potential strategies. Moreover, systematically summarized corresponding drugs application clinical trials. By integrating basic research findings, discussed current opportunities challenges

Language: Английский

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Interfacing with the Brain: How Nanotechnology Can Contribute

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Interfacing artificial devices with the human brain is central goal of neurotechnology. Yet, our imaginations are often limited by currently available paradigms and technologies. Suggestions for brain-machine interfaces have changed over time, along technology. Mechanical levers cable winches were used to move parts during mechanical age. Sophisticated electronic wiring remote control arisen age, ultimately leading plug-and-play computer interfaces. Nonetheless, brains so complex that these visions, until recently, largely remained unreachable dreams. The general problem, thus far, most technology mechanically and/or electrically engineered, whereas a living, dynamic entity. As result, worlds difficult interface one another. Nanotechnology, which encompasses engineered solid-state objects integrated circuits, excels at small length scales single few hundred nanometers and, thus, matches sizes biomolecules, biomolecular assemblies, cells. Consequently, we envision nanomaterials nanotools as opportunities in alternative ways. Here, review existing literature on use nanotechnology look forward discussing perspectives limitations based authors' expertise across range complementary disciplines─from neuroscience, engineering, physics, chemistry biology medicine, science mathematics, social jurisprudence. We focus but also include information from related fields when useful complementary.

Language: Английский

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Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

Autophagy, Journal Year: 2020, Volume and Issue: 17(4), P. 872 - 887

Published: March 6, 2020

Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, potent inducer antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), transcriptional factor controls expression multiple detoxifying enzymes through response elements (AREs), proposed target SFN. gene TFEB (transcription EB), master regulator autophagic lysosomal functions, which we show here to be potently activated by SFN induces nuclear translocation via Ca2+-dependent MTOR (mechanistic rapamycin kinase)-independent mechanism moderate increase reactive oxygen species (ROS). Activated then boosts genes required for autophagosome lysosome biogenesis, known facilitate clearance damaged mitochondria. Notably, activity SFN-induced protection against both acute oxidant bursts chronic stress. Hence, simultaneously activating macroautophagy/autophagy pathways, natural may trigger self-defense can effectively commonly associated with many metabolic age-related diseases.Abbreviations: ANOVA: analyzes variance; AREs: elements; Baf-A1: bafilomycin A1; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated regulation; DCFH-DA: 2',7'-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch ECH protein KO: knockout; LAMP1: membrane MCOLN1/TRPML1: mucolipin ML-SA1: mucolipin-specific synthetic agonist ML-SI3: inhibitor 3; MTOR: mechanistic kinase; MTORC1: kinase complex NAC: N-acetylcysteine; NFE2L2/NRF2: factor: 2; NPC: Niemann-Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: phosphatase Q-PCR: real time polymerase chain reaction; ROS: species; RPS6KB1/S6K1/p70S6K: ribosomal S6 B1; SFN: sulforaphane; TFEB: transcription EB; WT, wild-type.

Language: Английский

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Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity

Trends in Cell Biology, Journal Year: 2019, Volume and Issue: 29(11), P. 876 - 887

Published: Oct. 11, 2019

Language: Английский

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