l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

Sancineto, Luca ; Ostacolo, Carmine ; Ortega-Alarcon, David (Universidad de Zaragoza) ; Jimenez-Alesanco, Ana (Universidad de Zaragoza) ; Ceballos-Laita, Laura ; Vega, Sonia ; Abian, Olga (Universidad de Zaragoza) ; Velazquez-Campoy, Adrian (Universidad de Zaragoza) ; Moretti, Silvia ; Dabrowska, Agnieszka ; Botwina, Pawel ; Synowiec, Aleksandra ; Kula-Pacurar, Anna ; Pyrc, Krzysztof ; Iraci, Nunzio ; Santi, Claudio

Resumen: The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutinl-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

Idioma: Inglés

DOI: 10.3390/molecules26196062

Año: 2021

Publicado en: Molecules 26, 19 (2021), 6062 [14 pp.]
ISSN: 1420-3049

Factor impacto JCR: 4.927 (2021)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 65 / 179 = 0.363 (2021) - Q2 - T2
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 114 / 297 = 0.384 (2021) - Q2 - T2

Factor impacto CITESCORE: 5.9 - Pharmacology, Toxicology and Pharmaceutics (Q2) - Biochemistry, Genetics and Molecular Biology (Q2)

Factor impacto SCIMAGO: 0.705 - Analytical Chemistry (Q1) - Drug Discovery (Q1) - Pharmaceutical Science (Q1) - Molecular Medicine (Q1) - Organic Chemistry (Q1) - Medicine (miscellaneous) (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)