Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Density functional theory and enzyme studies support interactions between angiotensin receptor blockers and angiotensin converting enzyme-2: Relevance to coronavirus 2019
Δημιουργός/Συγγραφέας:	Apostolopoulos, Vasso Georgiou, Nikitas [EL] Τζέλη, Δήμητρα[EN] Tzeli, Demeter [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas Moore, Graham J Kelaidonis, Konstantinos Matsoukas, Minos-Timotheos Tsiodras, Sotirios Swiderski, Jordan Kate Gadanec, Laura Zulli, Anthony [EL] Χασάπης, Χρήστος[EN] Chasapis, Christos Matsoukas, John M
Ημερομηνία:	2024-06-28
Γλώσσα:	Αγγλικά
ISSN:	00452068
DOI:	10.1016/j.bioorg.2024.107602
Άλλο:	38959647
Περίληψη:	The binding affinities and interactions between eight drug candidates, both commercially available (candesartan; losartan; losartan carboxylic acid; nirmatrelvir; telmisartan) and newly synthesized benzimidazole-N-biphenyltetrazole (ACC519T), benzimidazole bis-N,N'-biphenyltetrazole (ACC519T(2) and 4-butyl-N,N-bis([2-(2H-tetrazol-5-yl)biphenyl-4-yl]) methyl (BV6), and the active site of angiotensin-converting enzyme-2 (ACE2) were evaluated for their potential as inhibitors against SARS-CoV-2 and regulators of ACE2 function through Density Functional Theory methodology and enzyme activity assays, respectively. Notably, telmisartan and ACC519T(2) exhibited pronounced binding affinities, forming strong interactions with ACE2's active center, favorably accepting proton from the guanidinium group of arginine273. The ordering of candidates by binding affinity and reactivity descriptors, emerged as telmisartan > ACC519T(2) > candesartan > ACC519T > losartan carboxylic acid > BV6 > losartan > nirmatrelvir. Proton transfers among the active center amino acids revealed their interconnectedness, highlighting a chain-like proton transfer involving tyrosine, phenylalanine, and histidine. Furthermore, these candidates revealed their potential antiviral abilities by influencing proton transfer within the ACE2 active site. Furthermore, through an in vitro pharmacological assays we determined that candesartan and the BV6 derivative, 4-butyl-N,N0-bis[20-2Htetrazol-5-yl)bipheyl-4-yl]methyl)imidazolium bromide (BV6(K+)2) also contain the capacity to increase ACE2 functional activity. This comprehensive analysis collectively underscores the promise of these compounds as potential therapeutic agents against SARS-CoV-2 by targeting crucial protein interactions.
Τίτλος πηγής δημοσίευσης:	Bioorganic chemistry
Τόμος/Κεφάλαιο:	150
Θεματική Κατηγορία:	[EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	Angiotensin-converting enzyme-2 Angiotensin receptor blockers Coronavirus 2019 Density functional theory Hypertension Proton transfer Severe acute respiratory syndrome coronavirus
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 The Authors. Published by Elsevier Inc.
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1016/j.bioorg.2024.107602
Εμφανίζεται στις συλλογές:	Ινστιτούτο Θεωρητικής και Φυσικής Χημείας (ΙΘΦΧ) - Επιστημονικό έργο