Fullerenol C60(OH)36: Antioxidant, Cytoprotective, Anti-Influenza Virus Activity, and Self-Assembly in Aqueous Solutions and Cell Culture Media

Viral infections and many other dangerous diseases are accompanied by the development of oxidative stress, which is a consequence of an increase in the level of the reactive oxygen species (ROS). In this regard, the search for effective antioxidants remains highly relevant. We tested fullerenol C₆₀(OH)₃₆ in the context of the connection between its self-assembly in aqueous solutions and cell culture media, antiradical activity, UV cytoprotective action, and antiviral activity against international reference strains of influenza virus A(H1N1)pdm09, A(H3N2), and B subtypes in vitro on the MDCK cell line. Various characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, NMR and ESR spectrometry, MALDI-TOF mass spectrometry, thermal analysis (TGA and DSC), dynamic light-scattering (DLS), and ζ-potential measurements, were used to confirm the production of fullerenol and study its self-assembly in aqueous solutions and cell culture media. Fullerenol C₆₀(OH)₃₆ demonstrated the ability to scavenge ^•DPPH, ^•OH, O₂^•- radicals and ¹O₂ and was non-toxic in the range of the studied concentrations (up to 200 μg/mL) when incubated with MDCK cells for 24 h. In addition, fullerenol exhibited a cytoprotective effect under UV irradiation (EC₅₀ = 29.7 ± 1.0 μM) and showed moderate activity against human influenza viruses of subtypes A(H1N1)pdm09 (SI = 9.9 ± 4.6) and A(H3N2) (SI = 12.5 ± 1.3) when determined by the hemagglutination assay (HA-test) and the MTT assay. At the same time, C₆₀(OH)₃₆ was ineffective in vitro against the actual strain of influenza B virus (Victoria lineage). The high bioavailability of fullerenol in combination with its cytoprotective effect, as well as its antiradical and antiviral activity combined with a relatively low toxicity, allows to consider it a promising compound for biomedical applications.