Malonic Acid-Type Fullerene Derivatives Strongly Inhibit The SARS-Cov-2 Main Protease

COVID-19 is a disease that is causing a global pandemic. There is an urgent need to develop new drugs to treat it. In this study, we evaluated the inhibitory activities of a series of fullerene derivatives against the main protease of SARS-CoV-2, the virus that causes COVID-19. As a result, it was found that the malonic acid-type fullerene derivatives showed strong inhibitory activities.

Hydrogenation of cage-opened C60 derivatives mediated by frustrated Lewis pairs

Multiply-carbonylated fullerene derivatives were found to work as one component in frustrated Lewis pairs which caused an Si–H bond activation in the presence of B(C6F5)3, leading to the carbonyl hydrogenation in up to 99% yield.

An Easily Synthesized Covalent Nanocage that Hosts Fullerenes in Multiple Charge States and Selectively Binds C70

Discrete nanocages provide a way to solubilize, separate, and tune the properties of molecular guests, including fullerenes and other aromatics. However, few such nanocages can be synthesized efficiently from inexpensive starting materials, limiting their practical utility. To address this limitation, we developed a new pyridinium-linked cofacial porphyrin nanocage (Cage4+) that can be prepared efficiently on a gram scale. NMR studies in CD3CN reveal that Cage4+ binds C60 and C70 with association constants >108 M-1 and complete selectivity for extracting C70 from mixtures of both fullerenes. The solubility of Cage4+ in polar solvents enabled electrochemical characterization of the host-guest complexes C60@Cage4+ and C70@Cage4+, finding that the redox properties of the encapsulated fullerenes are minimally affected despite the positive charge of the host. Complexes of the −1 and −2 charge states of the fullerenes bound in Cage4+ were subsequently characterized by UV-vis-NIR and NMR spectroscopies. The relatively easy preparation of Cage4+ and its ability to bind fullerenes without substantially affecting their redox properties suggests that C60@Cage4+ and C70@Cage4+ may be directly useful as solubilized fullerene derivatives.

Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives’ action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C70 derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C70 derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription—without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives’ oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.