Identification and evaluation of antiviral activity of novel compounds targeting SARS-CoV-2 virus by enzymatic and antiviral assays, and computational analysis

Autor: Ivana Nemčovičová, Katarína Lopušná, Iveta Štibrániová, Fabio Benedetti, Federico Berti, Fulvia Felluga, Sara Drioli, Mattia Vidali, Jaroslav Katrlík, Lucia Pažitná, Alena Holazová, Jana Blahutová, Simona Lenhartová, Monika Sláviková, Boris Klempa, Miroslav Ondrejovič, Daniela Chmelová, Barbora Legerská, Stanislav Miertuš, Mária Klacsová, Daniela Uhríková, Lukáš Kerti, Vladimír Frecer
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 39, Iss 1 (2024)
Druh dokumentu: article
ISSN: 14756366
1475-6374
1475-6366
DOI: 10.1080/14756366.2024.2301772
Popis: AbstractThe viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases Mpro and PLpro became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC) and identify potential antiviral compounds. Three compounds were found to be effective in reducing the SARS-CoV-2 load, with EC50 values in the low micromolar concentration range. However, these compounds also exhibited inhibitory activity IC50 against PLpro at approximately 10-fold higher micromolar concentrations. Although originally developed as PLpro inhibitors, the comparison between IC50 and EC50 of BBC indicates that the mechanism of their in vitro antiviral activity is probably not directly related to inhibition of viral cysteine proteases. In conclusion, our study has identified new potential noncytotoxic antiviral compounds suitable for in vivo testing and further improvement.
Databáze: Directory of Open Access Journals
Externí odkaz: