Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants.

The COVID-19 pandemic, which started in Wuhan, China, has spread rapidly over the world with no known antiviral therapy or vaccine. Interestingly, traditional Chinese medicine helped in flattening the pandemic curve in China. In this study, molecules from African medicinal plants were analysed as potential candidates against multiple SARS-CoV-2 therapeutic targets. Sixty-five molecules from the ZINC database subset (AfroDb Natural Products) were virtually screened with some reported repurposed therapeutics against six SARS-CoV-2 and two human targets. Molecular docking, druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the best hits were further simulated. Of the 65 compounds, only three, namely, 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside found in almond (), grape (), and common verbena (), were able to bind to all eight targets better than the reported repurposed drugs. The findings suggest these molecules may play a role as therapeutic leads in tackling this pandemic due to their multitarget activity

Model Optimization and In Silico Analysis of Potential Dipeptidyl Peptidase IV Antagonists from GC-MS Identified Compounds in Leaf Extracts.

Dipeptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes. Inhibitors of this enzyme constitute a new class of drugs used in the treatment and management of type 2 diabetes. In this study, phytocompounds in (NL) leaf extracts, identified using gas chromatography-mass spectroscopy (GC-MS), were tested for potential antagonists of DPP-IV via in silico techniques. Phytocompounds present in aqueous (NLA) and ethanol (NLE) leaf extracts were identified using GC-MS. DPP-IV model optimization and molecular docking of the identified compounds/standard inhibitors in the binding pocket was simulated. Drug-likeness, pharmacokinetic and pharmacodynamic properties of promising docked leads were also predicted. Results showed the presence of 50 phytocompounds in NL extracts of which only 2--p-methylphenyl-1-thio-β-d-glucoside, 3-tosylsedoheptulose, 4-benzyloxy-6-hydroxymethyl-tetrahydropyran-2,3,5-triol and vitamin E exhibited comparable or better binding iGEMDOCK and AutoDock Vina scores than the clinically prescribed standards. These four compounds exhibited promising drug-likeness as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties suggesting their candidature as novel leads for developing DPP-IV inhibitors

Model Optimization and In Silico Analysis of Potential Dipeptidyl Peptidase IV Antagonists from GC-MS Identified Compounds in Nauclea latifolia Leaf Extracts

Dipeptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes. Inhibitors of this enzyme constitute a new class of drugs used in the treatment and management of type 2 diabetes. In this study, phytocompounds in Nauclea latifolia (NL) leaf extracts, identified using gas chromatography–mass spectroscopy (GC-MS), were tested for potential antagonists of DPP-IV via in silico techniques. Phytocompounds present in N. latifolia aqueous (NLA) and ethanol (NLE) leaf extracts were identified using GC–MS. DPP-IV model optimization and molecular docking of the identified compounds/standard inhibitors in the binding pocket was simulated. Drug-likeness, pharmacokinetic and pharmacodynamic properties of promising docked leads were also predicted. Results showed the presence of 50 phytocompounds in NL extracts of which only 2-O-p-methylphenyl-1-thio-β-d-glucoside, 3-tosylsedoheptulose, 4-benzyloxy-6-hydroxymethyl-tetrahydropyran-2,3,5-triol and vitamin E exhibited comparable or better binding iGEMDOCK and AutoDock Vina scores than the clinically prescribed standards. These four compounds exhibited promising drug-likeness as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties suggesting their candidature as novel leads for developing DPP-IV inhibitors

Type 2 Diabetes Mellitus Mediation by the Disruptive Activity of Environmental Toxicants on Sex Hormone Receptors: In Silico Evaluation

This study investigates the disruptive activity of environmental toxicants on sex hormone receptors mediating type 2 diabetes mellitus (T2DM). Toxicokinetics, gene target prediction, molecular docking, molecular dynamics, and gene network analysis were applied in silico techniques. From the results, permethrin, perfluorooctanoic acid, dichlorodiphenyltrichloroethane, O-phenylphenol, bisphenol A, and diethylstilbestrol were the active toxic compounds that could modulate androgen (AR) and estrogen-α and –β receptors (ER) to induce T2DM. Early growth response 1 (EGR1), estrogen receptor 1 (ESR1), and tumour protein 63 (TP63) were the major transcription factors, while mitogen-activated protein kinases (MAPK) and cyclin-dependent kinases (CDK) were the major kinases upregulated by these toxicants via interactions with intermediary proteins such as PTEN, AKT1, NfKβ1, SMAD3 and others in the gene network analysis to mediate T2DM. These toxicants pose a major challenge to public health; hence, monitoring their manufacture, use, and disposal should be enforced. This would ensure reduced interaction between people and these toxic chemicals, thereby reducing the incidence and prevalence of T2DM

Data on antioxidant, hypolipidemic and hepatoprotective potential of (Benn.) Benth leaves.

This data article reports on the biochemical activity of ethanolic extract of (Benn.) Benth leaves (ETD) in male Wistar rats at an oral dose of 500-1500 mg/kg daily for 14 days. Control groups were administered distilled water and Vitamin C (10 mg/kg; b.wt). Indices of oxidative stress, dyslipidemia, liver injury and liver pathology were estimated in the plasma and organs after the investigation period. Oral treatment with ETD increased organ superoxide dismutase (SOD) activity, renal reduced glutathione (GSH) and plasma high density lipoprotein (HDL) concentrations while reducing plasma alanine transaminase (ALT) activity, plasma cholesterol (CHOL), bilirubin (DBIL) and organ malondialdehyde (MDA) concentrations (<0.05). Data was supported by histological report showing no pathologic abnormality. This data indicate ethanolic extract of leaves shows antioxidant, hypolipidemic and hepatoprotective potential

Data on in vivo antioxidant, hypolipidemic and hepatoprotective potential of Thaumatococcus daniellii (Benn.) Benth leaves

This data article reports on the in vivo biochemical activity of ethanolic extract of Thaumatococcus daniellii (Benn.) Benth leaves (ETD) in male Wistar rats at an oral dose of 500–1500 mg/kg daily for 14 days. Control groups were administered distilled water and Vitamin C (10 mg/kg; b.wt). Indices of oxidative stress, dyslipidemia, liver injury and liver pathology were estimated in the plasma and organs after the investigation period. Oral treatment with ETD increased organ superoxide dismutase (SOD) activity, renal reduced glutathione (GSH) and plasma high density lipoprotein (HDL) concentrations while reducing plasma alanine transaminase (ALT) activity, plasma cholesterol (CHOL), bilirubin (DBIL) and organ malondialdehyde (MDA) concentrations (P<0.05). Data was supported by histological report showing no pathologic abnormality. This data indicate ethanolic extract of T. daniellii leaves shows antioxidant, hypolipidemic and hepatoprotective potential. Keywords: Thaumatococcus daniellii, in vivo, Oxidative stress, Antioxidant, Liver injury, Hypolipidemi

Antidiabetic Activities of <em>Terminalia</em> Species in Nigeria

Terminalia species are well recognised in traditional medicine. They are known for producing fruits and nuts which are edible and possess pharmacotherapeutic properties. They also have ornamental purposes in urban areas where they are found. These species are used by traditional healers in the treatment and management of diabetes mellitus, its complications and other related ailments that are involved in the pathophysiological process of this disease. Research has been extensively done to validate these antidiabetic claims scientifically as well as understand the mechanism and mode of antidiabetic action. This chapter proposes to highlight the antidiabetic activities of Terminalia species found in Nigeria