Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds

Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant...

Descripción completa

Detalles Bibliográficos
Autores: Rizzuti, Bruno, Ceballos-Laita, Laura, Ortega-Alarcón, David, Jiménez-Alesanco, Ana, Vega, Sonia, Grande, Fedora, Conforti, Filomena, Abian, Olga, Velázquez-Campoy, Adrián
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/253466
Acceso en línea:http://hdl.handle.net/10261/253466
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
Main protease
Eugenol
Drug selection
Enzyme inhibitors
Antivirals
Spectroscopy
Molecular modeling
Descripción
Sumario:Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds