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

Rizzuti, Bruno ; Ceballos-Laita, Laura ; Ortega-Alarcon, David (Universidad de Zaragoza) ; Jimenez-Alesanco, Ana (Universidad de Zaragoza) ; Vega, Sonia ; Grande, Fedora ; Conforti, Filomena ; Abian, Olga (Universidad de Zaragoza) ; Velazquez-Campoy, Adrian (Universidad de Zaragoza)

Resumen: 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 \u03bcM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 \u03bcM), 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.

Idioma: Inglés

DOI: 10.3390/ph14090892

Año: 2021

Publicado en: Pharmaceuticals 14, 9 (2021), 892 [10 pp.]
ISSN: 1424-8247

Factor impacto JCR: 5.215 (2021)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 69 / 279 = 0.247 (2021) - Q1 - T1
Categ. JCR: CHEMISTRY, MEDICINAL rank: 16 / 63 = 0.254 (2021) - Q2 - T1

Factor impacto CITESCORE: 4.0 - Pharmacology, Toxicology and Pharmaceutics (Q2) - Biochemistry, Genetics and Molecular Biology (Q3)

Factor impacto SCIMAGO: 0.851 - Pharmaceutical Science (Q1) - Drug Discovery (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)