2. Academic Validation
  3. In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study

In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study

  • Biomolecules. 2021 Dec 10;11(12):1858. doi: 10.3390/biom11121858.
Damiano Cirri 1 2,  Tiziano Marzo 3,  Iogann Tolbatov 4,  Alessandro Marrone 5,  Francesco Saladini 6,  Ilaria Vicenti 6,  Filippo Dragoni 6,  Adele Boccuto 6,  Luigi Messori 2
Affiliations

Affiliations

  • 1 Laboratory of Metals in Medicine (MetMed), Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
  • 2 Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy.
  • 3 Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy.
  • 4 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.
  • 5 Dipartimento di Farmacia, Università "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy.
  • 6 Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.
PMID: 34944502 DOI: 10.3390/biom11121858
Abstract

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.

Keywords

COVID-19; SARS-CoV-2; antimony; antiviral drugs; auranofin; gold; metallodrugs; ruthenium; titanium; viral infection.

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