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

Autor: Jones LM; Department of Materials and The Henry Royce Institute, The University of Manchester, Manchester M19 3PL, United Kingdom., Super EH; Department of Materials and The Henry Royce Institute, The University of Manchester, Manchester M19 3PL, United Kingdom., Batt LJ; Department of Materials and The Henry Royce Institute, The University of Manchester, Manchester M19 3PL, United Kingdom., Gasbarri M; Institute of Materials, Interfaculty Bioengineering Institute, MXG 030 Lausanne, Switzerland., Coppola F; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Bhebhe LM; Department of Materials and The Henry Royce Institute, The University of Manchester, Manchester M19 3PL, United Kingdom., Cheesman BT; Aqdot Limited, Iconix Park, London Road, Pampisford, Cambridge CB22 3EG, United Kingdom., Howe AM; Aqdot Limited, Iconix Park, London Road, Pampisford, Cambridge CB22 3EG, United Kingdom., Král P; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States.; Department of Physics and Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Coulston R; Aqdot Limited, Iconix Park, London Road, Pampisford, Cambridge CB22 3EG, United Kingdom., Jones ST; Department of Materials and The Henry Royce Institute, The University of Manchester, Manchester M19 3PL, United Kingdom.
Jazyk: angličtina
Zdroj: ACS infectious diseases [ACS Infect Dis] 2022 Oct 14; Vol. 8 (10), pp. 2084-2095. Date of Electronic Publication: 2022 Sep 05.
DOI: 10.1021/acsinfecdis.2c00186
Abstrakt: 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.
Databáze: MEDLINE
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