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Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants |
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| Authors: | Taylor M Page Chuanxiong Nie Lenard Neander Tatyana L Povolotsky Anil Kumar Sahoo Philip Nickl Julia M Adler Obida Bawadkji Jörg Radnik Katharina Achazi Kai Ludwig Daniel Lauster Roland R Netz Jakob Trimpert Benedikt Kaufer Rainer Haag Ievgen S Donskyi |
| Affiliation: | 1. Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany;2. Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Physics Department, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany;3. Physics Department, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany;4. Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany BAM – Federal Institute for Material Science and Testing, Division of Surface Analysis and Interfacial Chemistry, Unter den Eichen 44–46, 12205 Berlin, Germany;5. Institut für Virologie, Freie Universität Berlin, Robert-von-Ostertag-Straße 7, 14163 Berlin, Germany;6. BAM – Federal Institute for Material Science and Testing, Division of Surface Analysis and Interfacial Chemistry, Unter den Eichen 44–46, 12205 Berlin, Germany;7. Forschungszentrum für Elektronenmikroskopie and Core Facility BioSupraMol, Freie Universität Berlin, Fabeckstraße 36A, 14195 Berlin, Germany;8. Institut für Virologie, Freie Universität Berlin, Robert-von-Ostertag-Straße 7, 14163 Berlin, Germany Tiermedizinischen Zentrum für Resistenzforschung (TZR), Freie Universität Berlin, 14163 Berlin, Germany |
| Abstract: | As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C60 fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously. |
| Keywords: | covalent functionalization fullerene SARS-CoV-2 sulfated materials virus inhibition |