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

Molecules

Nunzio Iraci¹  Carmine Ostacolo²  Silvia Moretti³  Luca Sancineto⁴  Claudio Santi⁴  Sonia Vega⁵  Adrian Velazquez-Campoy⁵  Ana Jimenez-Alesanco⁵  David Ortega-Alarcon⁵  Olga Abian⁵  Laura Ceballos-Laita⁵  Anna Kula-Pacurar⁶  Agnieszka Dabrowska⁶  Pawel Botwina⁶  Aleksandra Synowiec⁶  Krzysztof Pyrc⁶ 

[1] Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy;Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy;Eco Tech Engeneering e Servizi Ambientali srl, Via Bruno Colli 4, 06135 Ponte San Giovanni, Italy;Group of Catalysis Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06122 Perugia, Italy;Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain;Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland;

关键词: rutin;    l-arginine;    SARS-CoV-2;    main protease;    quercetin;   

DOI  :  10.3390/molecules26196062

来源: DOAJ

【 摘 要 】

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 rutin/l-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.

【 授权许可】

Unknown