Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease.

ZED1227 is a small molecule tissue transglutaminase (TG2) inhibitor. The compound selectively binds to the active state of TG2, forming a stable covalent bond with the cysteine in its catalytic center. The molecule was designed for the treatment of celiac disease. Celiac disease is an autoimmune-mediated chronic inflammatory condition of the small intestine affecting about 1-2% of people in Caucasian populations. The autoimmune disease is triggered by dietary gluten. Consumption of staple foods containing wheat, barley, or rye leads to destruction of the small intestinal mucosa in genetically susceptible individuals, and this is accompanied by the generation of characteristic TG2 autoantibodies. TG2 plays a causative role in the pathogenesis of celiac disease. Upon activation by Ca2+, it catalyzes the deamidation of gliadin peptides as well as the crosslinking of gliadin peptides to TG2 itself. These modified biological structures trigger breaking of oral tolerance to gluten, self-tolerance to TG2, and the activation of cytotoxic immune cells in the gut mucosa. Recently, in an exploratory proof-of-concept study, ZED1227 administration clinically validated TG2 as a "druggable" target in celiac disease. Here, we describe the specific features and profiling data of the drug candidate ZED1227. Further, we give an outlook on TG2 inhibition as a therapeutic approach in indications beyond celiac disease.

The need for fully bio-based facemasks to counter coronavirus outbreaks: A perspective.

The onset of coronavirus pandemic has sparked a shortage of facemasks in almost all nations. Without this personal protective equipment, healthcare providers, essential workers, and the general public are exposed to the risk of infection. In light of the aforementioned, it is critical to balance the supply and demand for masks. COVID-19 will also ensure that masks are always considered as an essential commodity in future pandemic preparedness. Moreover, billions of facemasks are produced from petrochemicals derived raw materials, which are non-degradable upon disposal after their single use, thus causing environmental pollution and damage. The sustainable way forward is to utilise raw materials that are side-stream products of local industries to develop facemasks having equal or better efficiency than the conventional ones. In this regard, wheat gluten biopolymer, which is a by-product or co-product of cereal industries, can be electrospun into nanofibre membranes and subsequently carbonised at over 700 °C to form a network structure, which can simultaneously act as the filter media and reinforcement for gluten-based masks. In parallel, the same gluten material can be processed into cohesive thin films using plasticiser and hot press. Additionally, lanosol, a naturally-occurring substance, imparts fire (V-0 rating in vertical burn test), and microbe resistance in gluten plastics. Thus, thin films of flexible gluten with very low amounts of lanosol (<10 wt%) can be bonded together with the carbonised mat and shaped by thermoforming to create the facemasks. The carbon mat acting as the filter can be attached to the masks through adapters that can also be made from injection moulded gluten. The creation of these masks could simultaneously be effective in reducing the transmittance of infectious diseases and pave the way for environmentally benign sustainable products.