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001-es BibID:	BIBFORM110635
035-os BibID:	(WoS)000985072100001 (Scopus)85151447550
Első szerző:	Kovács Tamás (általános orvos)
Cím:	Veklury (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content / Kovacs Tamas, Kurtan Kitti, Varga Zoltan, Nagy Peter, Panyi Gyorgy, Zakany Florina
Dátum:	2023
ISSN:	0007-1188
Megjegyzések:	Background and Purpose: Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID-19 therapy. Possible contributions of the vehicle, sulfobutylether-β-cyclodextrin (SBECD) to Veklury® effects have been overlooked. The powder and solution formulations of Veklury® are treated equivalently despite their different vehicle content. Our objective was to study Veklury® effects on initial membrane-coupled events of SARS-CoV-2 infection focusing on the cholesterol depletion-mediated role of SBECD. Experimental Approach: Using time-correlated flow cytometry and quantitative three-dimensional confocal microscopy, we studied early molecular events of SARS-CoV-2?host cell membrane interactions. Key Results: Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced binding of the spike receptor-binding domain (RBD) to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector along with remdesivir due to its cholesteroldepleting potential. Veklury® solution inhibited RBD binding more efficiently due to its twice higher SBECD content. The CD-induced inhibitory effects were more prominent at lower RBD concentrations and in cells with lower endogenous ACE2 expression, indicating that the supportive CD actions can be even more pronounced during in vivo infection when viral load and ACE expression are typically low. Conclusion and Implications: Our findings call for the differentiation of Veklury® formulations in meta-analyses of clinical trials, potentially revealing neglected benefits of the solution formulation, and also raise the possibility of adjuvant cyclodextrin (CD) therapy, even at higher doses, in COVID-19.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk cholesterol cyclodextrin remdesivir SARS-CoV-2 spike glycoprotein
Megjelenés:	British Journal Of Pharmacology. - 180 : 16 (2023), p. 2064-2084. -
További szerzők:	Kurtán Kitti (2000-) Varga Zoltán (1969-) (biofizikus, szakfordító) Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:	ANN133421 OTKA OTKA FK143400 OTKA K132906 OTKA K138075 OTKA K143071 OTKA UNKP-21-4-II-DE- 137 Egyéb UNKP-21-4-II-DE-138 Egyéb EFOP-3.6.2-16-2017-00006 Egyéb GINOP-2.3.2-15-2016-00015 Egyéb UNKP-22-4-II-DE-69 Egyéb
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001-es BibID:	BIBFORM129343
035-os BibID:	(WoS)001420209400001 (Scopus)85217760506
Első szerző:	Szabó Máté (általános orvos)
Cím:	Look Beyond Plasma Membrane Biophysics : revealing Considerable Variability of the Dipole Potential Between Plasma and Organelle Membranes of Living Cells / Mate Szabo, Bence Cs. Szabo, Kitti Kurtan, Zoltan Varga, Gyorgy Panyi, Peter Nagy, Florina Zakany, Tamas Kovacs
Dátum:	2025
ISSN:	1661-6596 1422-0067
Megjegyzések:	Due to the lack of measurement techniques suitable for examining compartments of intact, living cells, membrane biophysics is almost exclusively investigated in the plasma membrane despite the fact that its alterations in intracellular organelles may also contribute to disease pathogenesis. Here, we employ a novel, easy-to-use, confocal microscopy-based approach utilizing F66, an environment-sensitive fluorophore in combination with fluorescent organelle markers and quantitative image analysis to determine the magnitude of the molecular order-related dipole potential in the plasma membrane and intracellular organelles of various tumor and neural cell lines. Our comparative analysis demonstrates considerable intracellular variations of the dipole potential that may be large enough to modulate protein functions, with an inward decreasing gradient on the route of the secretory/endocytic pathway (plasma membrane >> lysosome > Golgi > endoplasmic reticulum), whereas mitochondrial membranes are characterized by a dipole potential slightly larger than that of lysosomes. Our approach is suitable and sensitive enough to quantify membrane biophysical properties selectively in intracellular compartments and their comparative analysis in intact, living cells, and, therefore, to identify the affected organelles and potential therapeutic targets in diseases associated with alterations in membrane lipid composition and thus biophysics such as tumors, metabolic, neurodegenerative, or lysosomal storage disorders.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk membrane biophysics membrane dipole potential intracellular organelles lysosome Golgi endoplasmic reticulum mitochondrion fluorescence microscopy
Megjelenés:	International Journal Of Molecular Sciences. - 26 : 3 (2025), p. 1-20. -
További szerzők:	Cs. Szabó Bence (1996-) (orvos) Kurtán Kitti (2000-) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus) Nagy Péter (1971-) (biofizikus) Zákány Florina (1989-) (általános orvos) Kovács Tamás (1985-) (általános orvos)
Pályázati támogatás:	FK146740, OTKA K143400 OTKA K138075 OTKA ANN133421 OTKA K132906 OTKA K143071 OTKA EKÖP-24-4-II-DE-74 Egyéb EKÖP-24-2-DE-205 Egyéb János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00392/23 MTA János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00676/24) MTA University of Debrecen Program for Scientific Publication Egyéb 2024-1.2.3-HU-RIZONT-2024-00099 Egyéb
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