Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors

[Display omitted] •Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets. Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC50 values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives. Further rational design of fullerene derivatives might lead to the development of compounds with further enhanced antiviral activity and decreased toxicity.