Therapeutic options for the highly pathogenic human coronavirus (HCoV) infections are urgently needed. Anticoronavirus therapy is however challenging, as coronaviruses are biologically diverse and rapidly mutating. In this work, the antiviral activity of seven different carbon quantum dots (CQDs) for the treatment of human coronavirus HCoV-229E infections was investigated. The first generation of antiviral CQDs was derived from hydrothermal carbonization of ethylenediamine/citric acid as carbon precursors and postmodified with boronic acid ligands. These nanostructures showed a concentration-dependent virus inactivation with an estimated EC 50 of 52 ± 8 μg mL −1 . CQDs derived from 4-aminophenylboronic acid without any further modification resulted in the second-generation of anti-HCoV nanomaterials with an EC 50 lowered to 5.2 ± 0.7 μg mL −1 . The underlying mechanism of action of these CQDs was revealed to be inhibition of HCoV-229E entry that could be due to interaction of the functional groups of the CQDs with HCoV-229E entry receptors; surprisingly, an equally large inhibition activity was observed at the viral replication step.
There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage. Although utilization of peptide covalent linkage onto hydrogels addresses partially this problem, the peptide release is commonly too slow. To alleviate these challenges, in this work, maleimidemodified antimicrobial peptides are covalently conjugated onto furan-based cryogel (CG) scaffolds via the Diels−Alder cycloaddition at room temperature. The furan group offers a handle for specific loading of the peptides, thus minimizing passive and burst drug release. The porous nature of the CG matrix provides rapid loading and release of therapeutic peptides, apart from high water uptake. Interfacing the peptide adduct containing a CG matrix with a reduced graphene oxide-modified Kapton substrate allows "on-demand" photothermal heating upon near-infrared (NIR) irradiation. A fabricated photothermal device enables tunable and efficient peptide release through NIR exposure to kill bacteria. Apart from spatial confinement offered by this CG-based bandage, the selective ablation of planktonic Staphylococcus aureus is demonstrated. It can be envisioned that this modular "on-demand" peptide-releasing device can be also employed for other topical applications by appropriate choice of therapeutic peptides.
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