Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Development of Triboelectroceutical Fabrics for Potential Applications in Self-Sanitizing Personal Protective Equipment.

Attachment of microbial bodies including the corona virus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a triboelectroceutical fabric (TECF) consisting of commonly available materials, namely, nylon and silicone rubber (SR), for the fabrication of protective gloves on the nitrile platform as model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and nylon on nitrile can generate more than 20 V transient or 41 µW output power, which is capable of charging a capacitor up to 65 V in only ∼50 s. The importance of the present work relies on the TECF-led antimicrobial activity through the generation of an electric current in saline water. The fabrication of TECF-based functional prototype gloves can generate hypochlorite ions through the formation of electrolyzed water upon rubbing them with saline water. Further, computational modelling has been employed to reveal the optimum structure and mechanistic pathway of antimicrobial hypochlorite generation. Detailed antimicrobial assays have been performed to establish effectiveness of such TECF-based gloves to reduce the risk from life-threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other materials with comparable properties, as a material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19.

ACE-2-Derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2.

SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields almost three-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide inhibitor of the novel coronavirus. The binding of the best peptide inhibitor with the spike protein is explored further by molecular dynamics, free energy, and principal component analysis, which demonstrate its efficacy compared to hACE-2. The delivery of the screened inhibitors with nanocarriers like metal-organic frameworks will be worthy of further consideration to boost their efficacy.

Bioinspired Spiky Peroxidase-Mimics for Localized Bacterial Capture and Synergistic Catalytic Sterilization.

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.