Discovery and Folding Dynamics of a Fused Bicyclic Cysteine Knot Undecapeptide from the Marine Sponge Halichondria bowerbanki.

We describe the discovery and structure of an undecapeptide natural product from a marine sponge, termed halichondamide A, that is morphed into a fused bicyclic ring topology via two disulfide bonds. Molecular dynamics simulations allow us to posit that the installation of one disulfide bond biases the intermediate peptide conformation and predisposes the formation of the second disulfide bond. The natural product was found to be mildly cytotoxic against liver and breast cancer cell lines.

A Common Insecticide Induced-Oxidative Stress in Wistar Rats: Significance for Humans and Implications for Nutritional Modulation of Insecticide Toxicity.

OBJECTIVE: This study examined the levels of selected micronutrients and associated biochemical changes in rats exposed to Baygon® insecticide. Arsenic is a toxic metalloid commonly used in insecticides manufacture but unheralded. METHODS: Fifteen rats, divided into three equal groups: Group I (control); group II (administered 2.5 mg/kg sodium arsenite (SA) on alternate days for four weeks); group III (exposed to 14.0 mL Baygon® m-3 cage volume daily for four weeks). Serum levels of arsenic (As), selenium (Se) and zinc (Zn) were determined using flame atomic absorption spectrophotometry (FAAS). Reduced glutathione (GSH), glutathione peroxidase (GPx), and total protein (TP) were determined spectrophotometrically. RESULTS: Arsenic and Se levels were significantly raised in groups II and III compared with control (p < 0.05), unlike Zn levels that were significantly decreased in groups II and III (p < 0.05) in both. No significant change in the activity of GPx; though the activity increased in the group treated with SA, but decreased in the group treated with Baygon® compared to control (P < 0.05). Histology of the liver and lung was unaltered in control, but in contrast, the SA-treated group demonstrated moderate fibrous hyperplasia with prominent highly infiltrated portal area in the liver; while the lung revealed thickened alveolar walls from proliferated pneumocytes. In the Baygon®-treated group, there was mild hyperplasia of the fibrous connective tissue and congested prominent portal areas; while the lung exhibited severe thickened alveolar walls due to proliferated pneumocytes. CONCLUSION: Exposure of rats to Baygon® elicited alteration of key trace elements involved in the antioxidant system, culminating in oxidative stress with attendant deleterious effects. One significance of this for humans is that it has great potentials for possible nutritional modulation of insecticide toxicity with micronutrients, especially with zinc, holding great promise in tropical developing countries.

Leaf paste of Telfairia occidentalis favourably modulates deleterious effects associated with exposure to diethylnitrosamine in male Wistar rats.

OBJECTIVES: Diethylnitrosamine (DEN) is found in workplaces, processed meats, tobacco smoke, whiskey, etc. It is capable of forming DNA-adducts. Fluted pumpkin (Telfairia occidentalis [To]) is a medicinal plant, and its herbal preparations have been employed variously in ethnomedicine. Furthermore, it has been reported to possess anti-oxidant, anti-cancer, anti-inflammatory properties. We investigated the possible mitigating effect of the leaf paste of To on DEN-induced deleterious effects in male Wistar rats. METHODS: Forty-five rats weighing between 100 and 150 g were equally divided into nine groups and treated thus: Group 1 (negative control), Group 2 (0.05 mg/kg carboxymethyl cellulose [CMC] daily), Group 3 (positive control, 25 mg/kg bw DEN administered intraperitoneally thrice per week), Group 4 (25 mg/kg bw quercetin [QUE] daily alone), Groups 5 and 6 (100 and 200 mg/kg bw To daily, respectively), Group 7 (25 mg/kg bw DEN and QUE), Groups 8 and 9 (25 mg/kg bw DEN with 100 and 200 mg/kg bw To, respectively). Blood glucose levels, liver damage biomarkers (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyltransferase [γ-GT]), frequency of micronucleated polychromatic erythrocyte (mPCEs), and liver histology were assessed. RESULTS: DEN significantly (p<0.05) increased blood glucose levels, activities of ALT, AST and γ-GT, and frequency of mPCEs. Histologically, DEN caused a severe architectural anarchy. However, the intervention groups demonstrated the remarkable protective properties of To by ameliorating the adverse effects caused by DEN. CONCLUSIONS: Taken together, the leaf paste of To is capable of mitigating DEN-induced hepatotoxicity and clastogenicity in male Wistar rats.

Assessment of intercontinents mutation hotspots and conserved domains within SARS-CoV-2 genome.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 pathogen, has led to waves of global pandemic claiming lives and posing a serious threat to public health and social cum physical interactions. To evaluate the mutational landscape and conserved regions in the genome of the causative pathogen, we analysed 7213 complete SARS-CoV-2 protein sequences mined from the Global Initiative on Sharing All Influenza Data (GISAID) repository from infected patients across all regions on the EpiCov web interface. Regions of origin and the corresponding number of sequences mined are as follows: Asia - 2487; Oceania - 2027; Europe - 1240; Africa - 717; South America - 391; and North America - 351. High recurrent mutations, namely: T265I in non-structural protein 2 (nsp2), L3606F in nsp6, P4715L in RNA-dependent RNA polymerase (RdRp), D614G in spike glycoprotein, R203K and G204R in nucleocapsid phosphoprotein and Q57H in ORF3a with well-conserved envelope and membrane proteins, 3CLpro and spike S2 domains across regions were observed. Comparative analyses of the viral sequences reveal the prevalence P4715L and D614G mutations as the most recurrent and concurrent in Africa (97.20%), Europe (89.83%) and moderately in Asia (61.60%). Mutation rates are central to viral transmissibility, evolution and virulence, which help them to invade host immunity and develop drug resistance. Based on the foregoing, it is important to understand the mutational spectra of SARS-CoV-2 genome across regions. This will help in identifying specific genomic sites as potential targets for drug design and vaccine development, monitoring the spread of the virus and unraveling its evolution, virulence and transmissibility.