Computer-Assisted Discovery of Salvia fruticosa Compounds With Schistosomicidal Activity.

Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant Salvia fruticosa. We virtually screened a library of 163 S fruticosa compounds by docking against Schistosoma mansoni sulfotransferase (SmSULT) using the PyRx software. Docking scores ranged from -4.7 to -9.3 kcal/mol. Compounds with binding affinity of -7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs.

Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe.

In this study, the concentrations of the essential elements to the human body N, K, Mg, P, Ca, Fe, Mn, and Zn of the fermented and non-fermented Fadogia ancylantha leaf samples were analysed to assess their nutritional value in two different areas in Zimbabwe: Mhangura (Mashonaland West, Province) and Alaska (Mashonaland West Province). Atomic absorption spectroscopy and ultraviolet spectrophotometry techniques were used to measure the concentrations of the minerals. The concentrations of manganese were significantly high (p < 0.05) in non-fermented treatments, with Mhangura samples having 0.447 mg/g and Alaska samples having 0.453 mg/g. Iron was high in fermented samples with Mhangura samples having 0.245 mg/g and Alaska samples having 0.270 mg/g. The concentrations of manganese and iron in Fadogia ancylantha can be used to supplement the recommended daily doses in pregnant, menstruating, and lactating women. The study, therefore, recommends that Fadogia ancylantha be used as a nutraceutical for the supplementation of iron and manganese.

Construction and analysis of protein-protein interaction networks based on nuclear proteomics data of the desiccation-tolerant Xerophyta schlechteri leaves subjected to dehydration stress.

In order to understand the mechanism of desiccation tolerance in Xerophyta schlechteri, we carried out an in silico study to identify hub proteins and functional modules in the nuclear proteome of the leaves. Protein-protein interaction networks were constructed and analyzed from proteome data obtained from Abdalla and Rafudeen. We constructed networks in Cytoscape using the GeneMania software and analyzed them using a Network Analyzer. Functional enrichment analysis of key proteins in the respective networks was done using GeneMania network enrichment analysis, and GO (Gene Ontology) terms were summarized using REViGO. Also, community analysis of differentially expressed proteins was conducted using the Cytoscape Apps, GeneMania and ClusterMaker. Functional modules associated with the communities were identified using an online tool, ShinyGO. We identified HSP 70-2 as the super-hub protein among the up-regulated proteins. On the other hand, 40S ribosomal protein S2-3 (a protein added by GeneMANIA) was identified as a super-hub protein associated with the down-regulated proteins. For up-regulated proteins, the enriched biological process terms were those associated with chromatin organization and negative regulation of transcription. In the down-regulated protein-set, terms associated with protein synthesis were significantly enriched. Community analysis identified three functional modules that can be categorized as chromatin organization, anti-oxidant activity and metabolic processes.

The computationally predicted drug-likeness, pharmacokinetics properties, medicinal chemistry parameters, and toxicity properties of Cucurbita maxima compounds.

Natural compounds are increasingly becoming an important source of drug leads for computer-aided drug design approaches. Cucurbita maxima has been observed to have medicinal properties and can, therefore, be a potential source of novel drug leads. However, before compounds can be synthesized in the lab for tests, modern approaches require that the candidate compounds be screened for drug-likeness characteristics and toxicity, among others. In this work, the computational tools, SwissADME and DataWarrior were used to screen C. maxima compounds for their potential consideration as drug leads. A total of 130 compounds, downloaded from the LOTUS natural products database, were computationally analysed. The data set presented in this work will be useful to researchers searching for novel drug leads based on natural compounds.

In Silico Study of Cucurbita maxima Compounds as Potential Therapeutics Against Schistosomiasis.

Schistosomiasis, a disease usually related to poverty and poor sanitation, affects more than 200 million people worldwide. Since the 1970s, the medical sector has depended on a single drug, praziquantel, for the treatment of the disease. The emerging evidence of resistance of the Schistosoma parasite to praziquantel and the drug's inefficacy against juvenile stages of the parasite makes the need to find alternative drugs an urgent matter. In this study, we explored the inhibition potential of compounds from Cucurbita maxima using molecular docking studies on Schistosoma mansoni purine nucleoside phosphorylase (SmPNP) and Schistosoma haematobium 28-kDa glutathione S-transferase (Sh28kDaGST). Following molecular docking studies and analysis of the active sites, the primary amino acids that were observed and shown to be involved in the SmPNP-ligand interaction are CYS 33, ARG 86, HIS 88, TYR 90, ALA 118, ALA 119, PRO 200, TYR 202, GLU 203, VAL 219, MET 221, THR 244, ASN 245, PRO 257 and HIS 259. For the Sh28dKa-ligand interaction, the primary amino acids were PHE 11, ARG 16, TRP 41, LEU 53, GLU 70 and SER 71. Momordicoside I aglycone binds to SmPNP with the lowest binding affinity of -7.9 kcal/mol by pi sigma bond interactions with HIS 88. Balsaminoside B binds to Sh28kDaGST with a binding affinity of -7.6 kcal/mol by hydrogen bond interaction with TRP 41, LEU 53 and SER 71. Pharmacokinetic studies showed favourable drug-like properties for the 10 compounds that exhibited the lowest binding energies. Therefore, we propose that bioactive compounds from C. maxima be considered as potential novel drug hits in the treatment of schistosomiasis.