In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study
Damiano Cirri,
Tiziano Marzo,
Iogann Tolbatov,
Alessandro Marrone,
Francesco Saladini,
Ilaria Vicenti,
Filippo Dragoni,
Adele Boccuto,
Luigi Messori
Affiliations
Damiano Cirri
Laboratory of Metals in Medicine (MetMed), Department of Chemistry “U. Schiff”, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy
Tiziano Marzo
Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy
Iogann Tolbatov
Institut de Chimie Moleculaire de l’Université de Bourgogne (ICMUB), UMR CNRS 6302, Université de Bourgogne Franche-Comté (UBFC), Avenue Alain Savary 9, 21078 Dijon, France
Alessandro Marrone
Dipartimento di Farmacia, Università “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy
Francesco Saladini
Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy
Ilaria Vicenti
Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy
Filippo Dragoni
Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy
Adele Boccuto
Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy
Luigi Messori
Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl3), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl3, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.
