Broad-Spectrum Extracellular Antiviral Properties of Cucurbit[n]urils

Luke M. Jones, Elana H. Super, Lauren J. Batt, Matteo Gasbarri, Francesco Coppola, Lorraine M. Bhebhe, Benjamin T. Cheesman, Andrew M. Howe, Petr Král, Roger Coulston, Samuel T. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortalities and morbidities worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a family of macrocycle chemical compounds 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 nontoxic 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 herpes simplex virus 2 (HSV-2), respiratory syncytial virus (RSV) and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n], having an antiviral effect against enveloped and nonenveloped species. High levels of efficacy were observed with 5 min 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 internalization 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.

Original languageEnglish
Pages (from-to)2084-2095
Number of pages12
JournalACS Infectious Diseases
Volume8
Issue number10
Early online date5 Sept 2022
DOIs
Publication statusPublished - 14 Oct 2022

Bibliographical note

Funding Information:
S.T.J. was funded by a Dame Kathleen Ollerenshaw Fellowship. L.M.J. was funded by an Innovate UK grant. A.M.H., B.T.C., and R.C. were partners on the same Innovate UK grant (IUK Project Reference 82583). L.J.B. was funded by the BBSRC with grant DTP3 2020-2025, reference BB/T008725/1. E.H.S. and L.M.B. were funded by an EPSRC DTP grant. M.G. was supported by the National Center of Competence in Research (NCCR) Bio-Inspired Materials. The authors would like to thank Francesco Stellacci at the Supramolecular NanoMaterials and Interfaces Laboratory in Switzerland for his help with all the SARS-CoV-2 related studies. The authors would also like to thank Prof. Pamela Vallely and Prof. Paul Klapper for their help with the supply of cell lines and viruses. The authors would also like to thank Dr. Lee Fielding and Elisabeth Trinh for generously providing bacterial DNA and the associated primers. Finally, the authors would also like to thank Dr. Nico Esselin for preparing the CB[ n] textiles.

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

Keywords

  • antiviral
  • cucurbituril
  • dose-response
  • macrocycle
  • virucidal
  • virustatic

ASJC Scopus subject areas

  • Infectious Diseases

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