Blessing Awoyemi

Research efforts for pancreatic cancer (PC) therapy has led to investigations of numerous therapeutic targets, yet there are still limited efficacy outcomes. In 2021, the annual PC cases of 508,533 resulted in mortality of 505,752 for both sexes according to GLOBOCAN. In order to address this burden, enhancer of zeste homolog 2 (EZH2); an epigenetic regulator implicated in various cancers, has been an attractive target, due to promising tumor-suppressive effects in both preclinical and clinical studies. This effect was observed from drugs that have strong affinity towards EZH2, but there is need to improve the structural moieties for better interaction towards this protein. In this study, we employed a structure-based drug discovery approach using CHEESE webserver for rapid ligand-based screening to identify and evaluate phytochemical derivatives for their potential to bind EZH2. Five phytochemicals, namely Moracin P, Naringenin 5-rhamnoside, Pinostrobin 5- glucoside, Phytocassane A, and Sakuranin with best performance against EZH2-PPARs from our previous study was used to generate top ten new derivatives each. The derivatives were subjected to molecular docking, pharmacokinetic, and toxicity predictions. The top-performing derivative interacting with EZH2 were further subjected to ADMET profiling with favorable pharmacokinetic, toxicity properties, and meeting key drug-likeness criteria. Molecular docking results revealed that several derivatives of Moracin P, Naringenin 5-rhamnoside, and Phytocassane A displayed higher predicted binding affinities (− 6.4 to − 8.2 Kcal/mol) compared to the parent template previously assessed for EZH2, engaging critical residues through hydrogen bonds and hydrophobic interactions. Molecular dynamic simulation (MDS) over 200 ns further confirmed the stability of selected protein-ligand complexes, with Moracin_P7 and Pinostrobin 5-glucoside_5 exhibiting high degrees flexibility within the first 100 ns, but remained stable for the last 100 ns, while contact analysis highlighted consistent interactions with the active site residues Gln653, Asp657, Asp664, Ser669, Asn673, Phe678, His711 and Tyr731. Conclusively, these findings provide evidence that CHEESE webserver is suitable to generate phytochemical derivatives that can be explored as feasible candidate in EZH2 inhibitory study and laying the groundwork for further in-vitro and in-vivo validation.

Edible insects (EI) are sustainable food sources, but with paradox that they serve as reservoirs of both microbial pathogens and health-promoting bioactive peptides. This duality presents both a challenge and an opportunity for food security, public health, and functional food innovation. Antimicrobial peptides (AMPs) from EI demonstrate potent activity, thus it could address issue of antimicrobial resistance. In addition, their structural diversity and low cytotoxicity make them promising candidates for nutraceuticals and peptide-based therapeutics. Moreover, EI farmed under suboptimal conditions can pose unknown risks, undermine consumer safety, and trust when inadequately processed or poorly regulated. This review addresses the paradox that EI represent both a potential source of microbial pathogen/parasite and a reservoir of health-promoting AMPs. In contrast to the earlier reviews that examine nutritional or antimicrobial properties individually, this article combines microbial risk management with peptide functionality and provided a biotechnological insight for the paradoxical balance between biosafety and bioactivity and point our attention to databases for AMPs curation, useful in peptide design and bioinformatics. Ultimately, advancing EI-derived AMPs in the global health system is possible, but it remains a challenge that requires transdisciplinary collaboration across biotechnology, food science, microbiology, immunology, science communicators, and policy makers. Graphical abstract