Genetic diversity and evolutionary analysis of Citrus Tristeza Virus p20 gene in Pakistan: insights into the spread and epidemiology

Background: Citrus tristeza virus (CTV) is a widespread disease and the most destruction causing agent of citrus. Pakistan is ranked amongst the top ten citrus producing countries around the globe and it contributes about 2% to its foreign exchange earnings. Based on this assumption it is very important to monitor and determine the evolutionary forces and the phylogeography of Pakistani CTV population.  Methods: A total of 49 sequences of p20 gene from Pakistan were phylogenetically compared with CTV sequences worldwide. These sequences were analyzed for their genetic diversity and evolution using a Bayesian Probability approach and predicted secondary structure.Results: Phylogenetic analysis using Bayesian probability inference and predicted secondary structures diversity of CTV indicated that Pakistani isolates were not diverse from global isolates. Lineage analysis showed that CTV was introduced in Pakistan in three individual events from various parts of the world.  After that CTV dispersed in Pakistan via vector transmission or by use of infected propagating material by local farmers.Conclusions: Our study confirmed multiple introductions of CTV in Pakistan and also confirmed the dissemination of CTV within Pakistan. This study also shows that the mutations are present in the predicted secondary structure of the p20 protein, however, it is not known if it affects the pathogenicity of the virus

Phytochemical Analyses for Antibacterial Activity and Therapeutic Compounds of Convolvulus arvensis L., Collected from the Salt Range of Pakistan

Background: Pharmaceutical world is currently facing a major issue of bacterial resistance against antibiotics. For the past few years, plants being an excellent source of phytochemicals have replaced many traditional antibacterial agents. Keeping this in view, the current study was conducted to detect the antibacterial activity and the presence of various phytochemicals in Convolvulus arvensis leaves and stem extracts.Methods: Eight different organic and aqueous extracts of Convolvulus arvensis L. (C. arvensis) leaves and stem were prepared and their antimicrobial activity against 13 clinically important bacterial species was investigated using the disc diffusion assay. Phytochemical screening of the aqueous extracts of C. arvensis was performed using qualitative tests.  Results: All the thirteen bacterial species tested in this study were found sensitive to the stem and leaf extracts of C. arvensis. Highest antimicrobial activity was observed against   Escherichia coli while among all the extracts butanol extract was the most effective antimicrobial agent. Phytochemical analyses using organic and aqueous extracts confirmed the presence of various secondary plant metabolites of therapeutic value i.e. saponins, flavonoids, steroids, tannins, phlobatannins, cardiac glycosides and coumarins.Conclusion: Our results indicate that C. arvensis plant contains some phytochemicals with antimicrobial affects. These chemicals possess great potential to be used as advanced therapeutic compounds against broad range of pathogenic bacteria

Genetic diversity and evolutionary analysis of Citrus Tristeza Virus p20 gene in Pakistan: insights into the spread and epidemiology

Background: Citrus tristeza virus (CTV) is a widespread disease and the most destruction causing agent of citrus. Pakistan is ranked amongst the top ten citrus producing countries around the globe and it contributes about 2% to its foreign exchange earnings. Based on this assumption it is very important to monitor and determine the evolutionary forces and the phylogeography of Pakistani CTV population. Methods: A total of 49 sequences of p20 gene from Pakistan were phylogenetically compared with CTV sequences worldwide. These sequences were analyzed for their genetic diversity and evolution using a Bayesian Probability approach and predicted secondary structure. Results: Phylogenetic analysis using Bayesian probability inference and predicted secondary structures diversity of CTV indicated that Pakistani isolates were not diverse from global isolates. Lineage analysis showed that CTV was introduced in Pakistan in three individual events from various parts of the world. After that CTV dispersed in Pakistan via vector transmission or by use of infected propagating material by local farmers. Conclusions: Our study confirmed multiple introductions of CTV in Pakistan and also confirmed the dissemination of CTV within Pakistan. This study also shows that the mutations are present in the predicted secondary structure of the p20 protein, however, it is not known if it affects the pathogenicity of the virus

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson's disease: a pharmacoinformatics study

Parkinson’s disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD.status: publishe

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study

International audienc

Pharmacoinformatics approach for investigation of alternative potential hepatitis C virus nonstructural protein 5B inhibitors

Hepatitis C virus (HCV) is one of the major viruses affecting the world today. It is a highly variable virus, having a rapid reproduction and evolution rate. The variability of genomes is due to hasty replication catalyzed by nonstructural protein 5B (NS5B) which is also a potential target site for the development of anti-HCV agents. Recently, the US Food and Drug Administration approved sofosbuvir as a novel oral NS5B inhibitor for the treatment of HCV. Unfortunately, it is much highlighted for its pricing issues. Hence, there is an urgent need to scrutinize alternate therapies against HCV that are available at affordable price and do not have associated side effects. Such a need is crucial especially in underdeveloped countries. The search for various new bioactive compounds from plants is a key part of pharmaceutical research. In the current study, we applied a pharmacoinformatics-based approach for the identification of active plant-derived compounds against NS5B. The results were compared to docking results of sofosbuvir. The lead compounds with high-binding ligands were further analyzed for pharmacokinetic and pharmacodynamic parameters based on in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile. The results showed the potential alternative lead compounds that can be developed into commercial drugs having high binding energy and promising ADMET properties.status: publishe

The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population - Fig 4

<p>(a) Maximum likelihood phylogeny of NS5B 381bp long fragment gene reconstructed for Pakistani sequence origin of genotype 3a (Highlighted in green) using (GTR+I+G) model. All samples GenBank accession numbers, countries of origin and years of sampling are shown. Individual clades are marked on the right. (b) A time-scaled phylogenetic tree estimated using NS5B 381bp long fragment gene of genotype 3a. Each branch is led by an isolate and is denoted by the following format: GenBank Accession number: Country: Date: Subtype. The branch lengths represent the evolutionary time that is measured by the grids corresponding to the timescale (years) shown at the tree base. The node labels represent the time of divergence of the respective node. To simplify the tree, the estimated 95% HPD are shown against MRCA and Pakistani clades only.</p

Are Low Lactose Concentrations a Risk Factor for <i>Staphylococcus aureus</i>-Associated Mastitis?

Staphylococcus aureus is a bacterium found in the milk of up to 38% of healthy lactating mothers; however, S. aureus is isolated with increased frequency from colostrum and mastitis milk. Both of these milk types have lower lactose concentrations compared to mature milk from healthy lactating mothers, which may indicate that lactose has a role in determining whether S. aureus can survive in human milk. The aim of this study was (1) to investigate whether the presence of S. aureus in human milk is associated with the milk’s lactose concentration, and (2) to determine whether different lactose concentrations can affect the ability of S. aureus isolates to grow in vitro. Human milk samples were collected at 10 weeks postpartum from mothers participating in the Drakenstein Child Health Study (Cape Town, South Africa) and underwent NMR spectroscopy to determine their metabolome. A subset of these samples (n = 117) was cultured to isolate S. aureus. Milk samples with lactose concentrations of less than 166 mM were more likely to have S. aureus present, compared to samples with lactose concentrations of over 166 mM (p S. aureus was negatively correlated with the lactose concentration of axenic culture. Lactose concentrations associated with human milk appear to have an inhibitory effect on the growth of S. aureus human milk isolates. Therefore, low-lactose human milk could potentially be a risk factor for increased S. aureus growth and the development of S. aureus-associated mastitis