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

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.

Polymersome-Encapsulated Chemosensors: New Design Strategies toward Biofluid-Applicable Cucurbit[7]uril Indicator Displacement Assays

“…Together, these observations confirm the successful encapsulation of the chemosensor. Serum albumins, including bovine serum albumin (BSA), human serum albumin (HSA), and insulin, constitute a category of proteins that impair the efficacy of CB7-based chemosensing ensembles by sequestering the macrocycle–dye complex within their protein pockets. − …”

“…Despite their unique properties as macrocyclic receptors, bimolecular cucurbit[7]­uril (CB7)-based chemosensing ensembles , (in the following referred to as chemosensors) are susceptible to deactivation in intricate, protein-rich biofluids, such as untreated serum samples, untreated urine, and within cells (Figure a). This is mainly due to the competition of the indicator molecules located in the host’s cavity with comparably very high concentrations of inorganic cations (>5 mM) and proteins (e.g., human serum albumin or insulin). − The nonspecific interaction with proteins can block the macrocycle cavity or disassemble the chemosensor, e.g., by competitive binding of the indicator dye, which renders it dysfunctional for the proposed detection of small biomolecules. Although we successfully employed unimolecular CB n -based chemosensors that function in high-salt buffers (10× PBS) as well as in human urine and saliva, − new design principles are needed to strengthen resistance to protein-mediated deactivation.…”

Pillararenes as Promising Carriers for Drug Delivery

“…Additionally, due to a wide range of binding motifs, pillararenes offer the potential to interact directly with viruses and inhibit infection, for instance, it was reported for human papillomavirus [ 119 ]. To date, the use of other macrocycles as antivirals is also limited by few examples [ 120 , 121 ], including a recent report on the inhibition of a large variety of viruses, including herpes simplex virus 2 (HSV-2), respiratory syncytial virus (RSV), and SARS-CoV-2, by cucurbit[n]urils via host–guest supramolecular interactions between viral surface proteins and the cavity of cucurbit[n]urils [ 122 ].…”

Antiviral mechanism change of poly(styrene sulfonate) through gold nanoparticle coating

“…This is regarded as the more favourable mode of action, as the virus is destroyed on contact, but it is often associated with greater cytotoxicity limiting its in vivo application. However, there have been reports, more recently, of materials with broad-spectrum virucidal properties with low cytoxicity including cycoldextrin, 25 cucurbit[n] urils, 22 dendrimers, 28 and nanoparticles. 30 Here, we report the synthesis of a HSPG-mimicking polymer and its use to functionalise AuNPs to form a virucidal material.…”