Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses
Δημιουργός/Συγγραφέας:	Ridgway, Harry Apostolopoulos, Vasso Moore, Graham J Gadanec, Laura Kate Zulli, Anthony Swiderski, Jordan Tsiodras, Sotirios Kelaidonis, Konstantinos [EL] Χασάπης, Χρήστος[EN] Chasapis, Christos Matsoukas, John M
Ημερομηνία:	2024-11-14
Γλώσσα:	Αγγλικά
ISSN:	1999-4915
DOI:	10.3390/v16111776
Άλλο:	39599890
Περίληψη:	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn2+) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2', suggesting interference with SARS-CoV-2's spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies.
Τίτλος πηγής δημοσίευσης:	Viruses
Τόμος/Κεφάλαιο:	16
Τεύχος:	11
Θεματική Κατηγορία:	[EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Επιδημίες. Επιδημιολογία[EN] Epidemics. Epidemiology [EL] Δομική Βιολογία[EN] Structural Biology [EL] Ιολογία[EN] Virology [EL] Βιοτεχνολογία[EN] Biotechnology
Λέξεις-Κλειδιά:	arginine blockers benzimidazole sartans bisartans coronavirus 2019 influenza pan-antivirals respiratory syncytial virus severe acute respiratory syndrome coronavirus 2
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/v16111776
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο