Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria.

Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure-function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.

Filamentous fungi for future functional food and feed.

In this review, we offer our opinion of current and expected trends regarding the use of mushrooms and mycelia in food and feed. Mushrooms have provided food for millennia and production methods and species diversity have recently expanded. Beyond mushrooms, cultured fungal mycelia are now harvested as a primary product for food. Mushrooms and mycelia provide dietary protein, lipids and fatty acids, vitamins, fibre, and flavour, and can improve the organoleptic properties of processed foods (including meat analogues). Further, they are often key ingredients in nutritional or therapeutic supplements because of diverse specialised metabolites. Mycelia can also improve feed conversion efficiency, gut health, and wellbeing in livestock. New molecular tools, coupled with quality genetic data, are improving production technologies, enabling the synthesis of specialised metabolites, and creating new processing and valorisation opportunities. Production systems for submerged culture are capital intensive, but investment is required considering the scale of the protein market.

Crude oil removal from aqueous solution using raw and carbonized Xanthoceras sorbifolia shells.

Fruit shell residue from Xanthoceras sorbifolia was investigated as a potential biosorbent to remove crude oil from aqueous solution. The shell powder and its carbonized material were compared while assessing various factors that influenced oil removal capacity. The structure and sorption mechanism were characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The oil removal capacity of the raw material (75.1 mg g-1) was better than the carbonized material (49.5 mg g-1). The oil removal capacity increased with greater saponin content, indicating that hydrophobic and lipophilic surface characteristics of the saponins improved adsorption by the raw X. sorbifolia shell. An orthogonal experimental design was used to optimize the adsorption. Using 4 g L-1 of raw X. sorbifolia shell (particle size of < 0.15 mm), the highest crude oil removal efficiency was obtained using an initial oil concentration of 400 mg L-1, adsorption temperature of 30 °C, adsorption time of 10 min at a shaking speed of 150 rpm. The adsorption of crude oil onto X. sorbifolia shell was best described using a pseudo-second-order kinetic model. Raw X. sorbifolia shell material was more efficient than the carbonized material at crude oil removal from aqueous solution. This was attributable to the functional groups of saponins in raw X. sorbifolia shell. This study highlights that some agricultural and forest residues could be a promising source of low-cost biosorbents for oil contaminants from water-without requiring additional processing such as carbonization.

Discovery of novel benzothienoazepine derivatives as potent inhibitors of respiratory syncytial virus.

The development of novel non-nucleoside inhibitors of the RSV polymerase complex is of significant clinical interest. Compounds derived from the benzothienoazepine core, such as AZ-27, are potent inhibitors of RSV viruses of the A-subgroup, but are only moderately active against the B serotype and as yet have not demonstrated activity in vivo. Herein we report the discovery of several novel families of C-2 arylated benzothienoazepine derivatives that are highly potent RSV polymerase inhibitors and reveal an exemplary structure, compound 4a, which shows low nanomolar activity against both RSV A and B viral subtypes. Furthermore, this compound is effective at suppressing viral replication, when administered intranasally, in a rodent model of RSV infection. These results suggest that compounds belonging to this chemotypes have the potential to provide superior anti-RSV agents than those currently available for clinical use.

Biochemistry of envenomation.

Venoms and toxins are of significant interest due to their ability to cause a wide range of pathophysiological conditions that can potentially result in death. Despite their wide distribution among plants and animals, the biochemical pathways associated with these pathogenic agents remain largely unexplored. Impoverished and underdeveloped regions appear especially susceptible to increased incidence and severity due to poor socioeconomic conditions and lack of appropriate medical treatment infrastructure. To facilitate better management and treatment of envenomation victims, it is essential that the biochemical mechanisms of their action be elucidated. This review aims to characterize downstream envenomation mechanisms by addressing the major neuro-, cardio-, and hemotoxins as well as ion-channel toxins. Because of their use in folk and traditional medicine, the biochemistry behind venom therapy and possible implications on conventional medicine will also be addressed.