Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity. Communicated by Ramaswamy H. SarmaHighlightsCoronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2.All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors.Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively, of SARS CoV-2.These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module.All the compounds showed drug-likeness properties.MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy.

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Medicinal plants containing complex mixtures of several compounds with various potential beneficial biological effects are attractive treatment interventions for a complex multi-faceted disease like diabetes. In this study, compounds identified from African medicinal plants were evaluated for their potential anti-diabetic activity. A total of 867 compounds identified from over 300 medicinal plants were screened in silico with the DIA-DB web server (http://bio-hpc.eu/software/dia-db/) against 17 known anti-diabetic drug targets. Four hundred and thirty compounds were identified as potential inhibitors, with 184 plants being identified as the sources of these compounds. The plants Argemone ochroleuca, Clivia miniata, Crinum bulbispermum, Danais fragans, Dioscorea dregeana, Dodonaea angustifolia, Eucomis autumnalis, Gnidia kraussiana, Melianthus comosus, Mondia whitei, Pelargonium sidoides, Typha capensis, Vinca minor, Voacanga Africana, and Xysmalobium undulatum were identified as new sources rich in compounds with a potential anti-diabetic activity. The major targets identified for the natural compounds were aldose reductase, hydroxysteroid 11-beta dehydrogenase 1, dipeptidyl peptidase 4, and peroxisome proliferator-activated receptor delta. More than 30% of the compounds had five or more potential targets. A hierarchical clustering analysis coupled with a maximum common substructure analysis revealed the importance of the flavonoid backbone for predicting potential activity against aldose reductase and hydroxysteroid 11-beta dehydrogenase 1. Filtering with physiochemical and the absorption, distribution, metabolism, excretion and toxicity (ADMET) descriptors identified 28 compounds with favorable ADMET properties. The six compounds-crotofoline A, erythraline, henningsiine, nauclefidine, vinburnine, and voaphylline-were identified as novel potential multi-targeted anti-diabetic compounds, with favorable ADMET properties for further drug development.

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Background Inflammation is a common risk factor in the pathogenesis of conditions such as infections, arthritis, type 2 diabetes mellitus, obesity and cancer. An ethnobotanical survey of medicinal plants used traditionally to treat inflammation and related disorders such as pain, arthritis and stomach aches in southern Africa led to the selection of 25 plant species used in this study. Methods The antioxidant activities of acetone extracts were determined by measuring the free radical scavenging activity and ferric reducing ability, respectively. The anti-inflammatory activities of the extracts were determined by measuring the inhibitory effect of the extracts on the activities of the pro-inflammatory enzyme, lipoxygenase and inducible nitric oxide synthase. Results Extracts of Peltophorum africanum had good antioxidant activity with IC50 values of 4.67 ± 0.31 μg/mL and 7.71 ± 0.36 μg/mL compared to that of the positive control ascorbic acid (2.92 ± 0.14 μg/mL and 13.57 ± 0.44 μg/mL), using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods, respectively. The metabolism of linoleic acid to leukotriene derivatives by 15-lipoxygenase (15-LOX) was also inhibited by the crude acetone extracts of Peltophorum africanum (IC50 = 12.42 μg/mL), Zanthoxylum capense (IC50 = 14.92 μg/mL) compared to the positive control quercetin (IC50 = 8.75 μg/mL). There was a poor correlation between the flavonoid content and 15-LOX inhibition by the extracts (R(2) = 0.05), indicating that flavonoids are not involved in LOX inhibition. Extracts of Clausena anisata, at a concentration of 6.25 μg/mL inhibited nitric oxide production by RAW 264.7 macrophage cell lines in vitro by 96 %. The extracts of Zanthoxylum capense were the least cytotoxic (IC50 > 1000 μg/mL) when the extract toxicity was determined against Vero (African green Monkey) kidney cell lines. Conclusion Some plant species used traditionally to treat pain have reasonable anti-inflammatory activity and flavonoids are probably not involved in this process.

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Aim of the study Eighteen plants were assessed for antimicrobial activity against pathogens associated with prevalent urogenital/sexually transmitted infections. Plant selection was based on information obtained from the ethnobotanical literature. Materials and methods Dried plant material was submerged in a 1:1 mixture of methanol and dichloromethane for 24 h. Aqueous extracts were prepared by submerging dried plant material in sterile distilled water for 24 h followed by lyophilization. Essential oils were distilled from the two aromatic plant species (Tarchonanthus camphoratus and Croton gratissimus). Antimicrobial activity was assessed using the micro-well minimum inhibitory concentration (MIC) assay with specific modifications to facilitate fastidious growth of pathogens. Results Tarchonanthus camphoratus (solvent extract) showed the most significant broad spectrum activity with MIC values ranging between 0.50 and 0.70 mg/ml against five of the six pathogens tested. Other noteworthy activity was found for Hypericum aethiopicum (root) at 0.3 mg/ml (Neisseria gonorrhoeae).Polygala fruticosa and the solvent root extract of Hypericum aethiopicum showed highest sensitivities towards Gardnerella vaginalis at 0.2 mg/ml. Efficacy of the solvent extracts against the pathogen Oligella ureolytica demonstrated antimicrobial activity (MIC values Conclusions Antimicrobial activity was observed for a number of the plant samples against at least one or more pathogen, thus validating the ethnobotanical use as an anti-infective to treat sexually transmitted diseases.

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Polygala fruticosa (P.J. Bergius) is one of the most popular medicinal plants in South Africa but to date there is no documented evidence corroborating its safety. This study thus aimed to determine the toxicity profile of the aqueous extract of Polygala fruticosa by determining its effects after acute and sub-chronic oral administration in female mice and rats, respectively. In adult mice, single oral administrations of the aqueous extract of Polygala fruticosa (2-20 g/kg body weight) induced an increase in the incidence of general behavioural adverse effects. The mortality rate also increases with increasing dosage (LD(50)=10.8 g/kg). In rats, daily single oral doses of Polygala fruticosa aqueous extract (0.1 and 1g/kg) were well tolerated behaviourally after 31 days of dosing (LD(50) much higher than 1g/kg) and induced no significant changes in body and organs weights. However, haematological and biochemical parameters showed a significant decrease in platelet count and significant increases in ALT, AST and creatinine levels suggesting disturbances of haemopoiesis, liver and kidney functions. Overall, the findings of this study indicate that Polygala fruticosa is non-toxic and has, at low dose, a low toxicity potential in acute and chronic oral administrations, respectively. However, at high chronic oral doses, Polygala fruticosa has significant anti-haemopoietic, hepatotoxic and nephrotoxic activities.

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