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  1. Pubblicazioni

Discovery of a Novel Trifluoromethyl Diazirine Inhibitor of SARS-CoV-2 Mpro

Articolo
Data di Pubblicazione:
2023
Abstract:
SARS-CoV-2 Mpro is a chymotrypsin-like cysteine protease playing a relevant role during the replication and infectivity of SARS-CoV-2, the coronavirus responsible for COVID-19. The binding site of Mpro is characterized by the presence of a catalytic Cys145 which carries out the hydrolytic activity of the enzyme. As a consequence, several Mpro inhibitors have been proposed to date in order to fight the COVID-19 pandemic. In our work, we designed, synthesized and biologically evaluated MPD112, a novel inhibitor of SARS-CoV-2 Mpro bearing a trifluoromethyl diazirine moiety. MPD112 displayed in vitro inhibition activity against SARS-CoV-2 Mpro at a low micromolar level (IC50 = 4.1  M) in a FRET-based assay. Moreover, an inhibition assay against PLpro revealed lack of inhibition, assuring the selectivity of the compound for the Mpro. Furthermore, the target compound MPD112 was docked within the binding site of the enzyme to predict the established intermolecular interactions in silico. MPD112 was subsequently tested on the HCT-8 cell line to evaluate its effect on human cells’ viability, displaying good tolerability, demonstrating the promising biological compatibility and activity of a trifluoromethyl diazirine moiety in the design and development of SARS-CoV-2 Mpro binders.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
SARS-CoV-2 Mpro, diazirines, coronavirus, SARS-CoV-2, COVID-19, cysteine proteases, enzymatic inhibitors
Elenco autori:
Citarella, Andrea; Moi, Davide; Pedrini, Martina; Pérez-Peña, Helena; Pieraccini, Stefano; Stagno, Claudio; Micale, Nicola; Schirmeister, Tanja; Sibille, Giulia; Gribaudo, Giorgio; Silvani, Alessandra; Passarella, Daniele; Giannini, Clelia
Autori di Ateneo:
GRIBAUDO Giorgio
SIBILLE GIULIA
Link alla scheda completa:
https://iris.unito.it/handle/2318/1885907
Link al Full Text:
https://iris.unito.it/retrieve/handle/2318/1885907/1070682/Citarella%20et%20al._Molecules_2023.pdf
Pubblicato in:
MOLECULES
Journal
Progetto:
Progetti PNRR M4C2 Iniziativa 1.3- PE13 INF-ACT: Adesione dell’Università degli Studi di Torino alla Fondazione "INF-ACT - One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Disease"
  • Dati Generali
  • Aree Di Ricerca

Dati Generali

URL

https://www.mdpi.com/1420-3049/28/2/514

Aree Di Ricerca

Settori (15)


LS6_6 - Infectious diseases - (2022)

LS6_9 - Antimicrobials, antimicrobial resistance - (2022)

PE5_18 - Medicinal chemistry - (2022)

CIBO, AGRICOLTURA e ALLEVAMENTI - Farmacologia Veterinaria

CIBO, AGRICOLTURA e ALLEVAMENTI - Patologia e malattie degli animali

CIBO, AGRICOLTURA e ALLEVAMENTI - Scienze cliniche veterinarie

MEDICINA, SALUTE e BENESSERE - Chimica e Salute

MEDICINA, SALUTE e BENESSERE - Epidemiologia

MEDICINA, SALUTE e BENESSERE - Oncologia e Tumori

MEDICINA, SALUTE e BENESSERE - Ricerca Traslazionale e Clinica

MEDICINA, SALUTE e BENESSERE - Trapianti e medicina rigenerativa

PIANETA TERRA, AMBIENTE, CLIMA, ENERGIA e SOSTENIBILITA' - Chimica e Ambiente

SCIENZE DELLA VITA e FARMACOLOGIA - Chimica Analitica e Farmaceutica

SCIENZE DELLA VITA e FARMACOLOGIA - Interazioni tra molecole, cellule, organismi e ambiente

SCIENZE MATEMATICHE, CHIMICHE, FISICHE - Materiali Avanzati
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