Powerful proteins from polyp possessing predators

Cnidarians are soft bodied animals possessing complex venom systems which have evolved to allow for the capture of arthropod and vertebrate prey, as well as to defend themselves against such predators. The effects of these venoms on humans, as a result of envenomation, has been studied for many decades, whereas the possibility of using these proteins to fight human disease is in its infancy. Drug discovery utilisation of Cnidarian venoms has been hampered by availability of animals and suitable extraction techniques that allow for study of such protein toxins. Studies of toxins that have been suitably purified for drug discovery have, by in large, only investigated target engagement and negated to investigate other drug like properties such as absorption, dispersion, metabolism, and excretion (ADME). This chapter will review the sourcing of Cnidaria for drug discovery, extraction of venom components, actions of venoms on drug relevant targets and their suitability as drug like molecules

Beauty from the deep: cnidarians in cosmetics

Cnidarian proteins are considered useful for the development of therapeutics, as well as this they have also received the attention of biotechnology and the cosmetic industries. In 2017 the first ever sea anemone venom peptide cosmetic, named SensAmone P5, was launched by Mibelle Biochemistry. This synthetic peptide is based on the interaction of APHC1, from Heteractis crispa, on the pain relevant ion channel TRPV1. This peptide reduces TRPV1 signalling in-vitro and skin sensitivity in human volunteers. Aside from venoms, jellyfish mucus and collagen are both used in cosmetic preparations. Many legal definitions of animals do not include the invertebrates and thus it is likely that invertebrate proteins are more acceptable as an alternative to mammalian proteins. Mucins are important proteins for moisturisers and using jellyfish as the source appears to be a suitable alternative to bovine and porcine proteins which were previously used. The main structural protein that supports the soft bodied jellyfish is collagen. This collagen appears to be biocompatible with human tissues and thus has been successful as a cosmetic, as well as being used in-vitro for 3D tissue engineering scaffolds. This short communication will discuss the use of Cnidarian proteins in cosmetics

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Kinome scale profiling of venom effects on cancer cells reveals potential new venom activities

The search for novel and relevant cancer therapeutics is continuous and ongoing. Cancer adaptations, resulting in therapeutic treatment failures, fuel this continuous necessity for new drugs to novel targets. Recently, researchers have started to investigate the effect of venoms and venom components on different types of cancer, investigating their mechanisms of action. Receptor tyrosine kinases (RTKs) comprise a family of highly conserved and functionally important druggable targets for cancer therapy. This research exploits the novelty of complex venom mixtures to affect phosphorylation of the epidermal growth factor receptor (EGFR) and related RTK family members, dually identifying new activities and unexplored avenues for future cancer and venom research. Six whole venoms from diverse species taxa, were evaluated for their ability to illicit changes in the phosphorylated expression of a panel of 49 commonly expressed RTKs. The triple negative breast cancer cell line MDA-MB-468 was treated with optimised venom doses, pre-determined by SDS PAGE and Western blot analysis. The phosphorylated expression levels of 49 RTKs in response to the venoms were assessed with the use of Human Phospho-RTK Arrays and analysed using ImageLab 5.2.1 analysis software (BioRad). Inhibition of EGFR phosphorylation occurred with treatment of venom from Acanthoscurria geniculata (Theraphosidae), Heterometrus swammerdami (Scorpionidae), Crotalus durissus vegrandis (Crotalidae) and Naja naja (Elapidae). Western green mamba Dendroaspis viridis venom increased EGFR phosphorylation. Eph, HGFR and HER were the most affected receptor families by venoms. Whilst the importance of these changes in terms of effect on MDA-MB-468 cells’ long-term viability and functionality are still unclear, the findings present exciting opportunities for further investigation as potential drug targets in cancer and as tools to understand better how these pathways interact

Full spectrum lighting induces behavioral changes and increases cortisol immunoreactivity in captive arachnids

The use of full spectrum illumination, including ultraviolet (UV), during captive husbandry of arachnids such as scorpions and theraphosids (tarantulas) is common practice in zoological institutions and amongst some hobbyists, as confirmed by a survey undertaken in this study. The effect of such lighting on captive arachnids has not been previously investigated. Comparison of key behavioral changes and haemolymph cortisol immunoreactivity was undertaken with and without full spectrum lighting. Two representative large arachnid species - king baboon spiders, Pelinobius muticus and Indian giant scorpions, Heterometrus swammerdami were selected for the study. Both organisms spent all their time hidden when exposed to full spectrum light compared to low-level ambient light except for one instance, in one spider, for one observation. There was no significant difference in burrowing and webbing in P. muticus when exposed to full spectrum lighting. There was a decrease in the number of behaviors or postures expressed in full spectrum lighting compared to ambient light for both species. Cortisol immunoactivity of both species were significantly elevated after exposure to full spectrum lighting compared to the same period of ambient light. This study provides the first evidence of detectable cortisol immunoactivity in arachnid haemolymph. These levels changed in response to full spectrum illumination and were linked to behaviorial changes. This suggests that a common husbandry practice may be detrimental to these animals