<span style="font-variant: small-caps">l</span>-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells
Luca Sancineto,
Carmine Ostacolo,
David Ortega-Alarcon,
Ana Jimenez-Alesanco,
Laura Ceballos-Laita,
Sonia Vega,
Olga Abian,
Adrian Velazquez-Campoy,
Silvia Moretti,
Agnieszka Dabrowska,
Pawel Botwina,
Aleksandra Synowiec,
Anna Kula-Pacurar,
Krzysztof Pyrc,
Nunzio Iraci,
Claudio Santi
Affiliations
Luca Sancineto
Group of Catalysis Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06122 Perugia, Italy
Carmine Ostacolo
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy
David Ortega-Alarcon
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Ana Jimenez-Alesanco
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Laura Ceballos-Laita
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Sonia Vega
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Olga Abian
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Adrian Velazquez-Campoy
Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI and GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain
Silvia Moretti
Eco Tech Engeneering e Servizi Ambientali srl, Via Bruno Colli 4, 06135 Ponte San Giovanni, Italy
Agnieszka Dabrowska
Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
Pawel Botwina
Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
Aleksandra Synowiec
Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
Anna Kula-Pacurar
Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
Krzysztof Pyrc
Malopolska Centre of Biotechnology, Virogenetics Laboratory of Virology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland
Nunzio Iraci
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
Claudio Santi
Group of Catalysis Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06122 Perugia, Italy
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.