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

Damiano Cirri,Iogann Tolbatov,Ilaria Vicenti,Adele Boccuto,Filippo Dragoni,Alessandro Marrone,Luigi Messori,Francesco Saladini,Tiziano Marzo

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.

Highlights

Introduction iationsThe outbreak and rapid spread of COVID-19, sometimes associated with severe symptoms requiring hospitalization, and, less frequently, with lethal complications, are posing dramatic problems to health systems worldwide [1], with serious consequences to social relationships and economic growth
Owing to our long experience in the field of metal-based drugs, we could quite straightforwardly establish a small panel of representative metal compounds that included many different metal centers, such as ruthenium, gold and titanium [23]
Metal compounds offer a rich variety of chemical structures and reactivities that merit to be considered in the screening libraries of chemical substances for new drug discovery [23]

Summary

Introduction

The outbreak and rapid spread of COVID-19, sometimes associated with severe symptoms requiring hospitalization, and, less frequently, with lethal complications, are posing dramatic problems to health systems worldwide [1], with serious consequences to social relationships and economic growth. Recent evidence indicates that treatment with the nucleoside analogue Molnupiravir reduced the risk of admission to hospital and death in non-hospitalized adults who had mild to moderate COVID-19 symptoms [4]. To this end, expanding the chemical space of Licensee MDPI, Basel, Switzerland.

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