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bioRxiv · 10.1101/2022.03.15.484424

Broad-spectrum extracellular antiviral properties of Cucurbiturils

Jones, L. M.·Super, E. H.·Batt, L. J.·Gasbarri, M.·Cheesman, B. T.·Howe, A. M.·Coulston, R.·Jones, S. T.
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Abstract

Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortality and morbidity worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a macrocycle chemical compound existing as a range of homologues; due to their structure they can bind to biological materials, acting as supramolecular "hosts" to "guests", such as amino acids. Due to the increasing need for a non-toxic antiviral compound, we investigated whether cucurbit[n]urils could act in an antiviral manner. We have found that certain cucurbit[n]uril homologues do indeed have an antiviral effect against a range of viruses, including RSV and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n] mixtures, having an antiviral effect against enveloped and non-enveloped species. High levels of efficacy were observed with five-minute contact times across different viruses. We also demonstrate that CB[7] acts with an extracellular virucidal mode of action via host-guest supramolecular interactions between viral surface proteins and the CB[n] cavity, rather than via cell internalisation or a virustatic mechanism. This finding demonstrates that CB[7] acts as a supramolecular virucidal antiviral (a mechanism distinct from other current extracellular antivirals) demonstrating the potential of supramolecular interactions for future antiviral disinfectants.

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Jones, L. M., Super, E. H., Batt, L. J., Gasbarri, M., Cheesman, B. T., Howe, A. M., Coulston, R., Jones, S. T.. 2022-03-15. Broad-spectrum extracellular antiviral properties of Cucurbiturils. https://doi.org/10.1101/2022.03.15.484424

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