Recent Development in Identification of Potential Novel Therapeutic Targets Against Trypanosomatids.

Trypanosomatids continue to cause suffering among human and wide range of animal population and have enormous health, social and economic impact. The present constraints in control of trypanosomosis are availability of limited number of effective drugs with narrow safety index, nonavailability of vaccines due to immune evasion mechanisms developed by the parasite and drug resistance problem. The kinetoplastids/ trypanosomatids possess unique kinetoplast DNA structure and express hundreds of membrane transport proteins that allow them to take up nutrients, establish ion gradients, efflux metabolites, translocate compounds from one intracellular compartment to another, and take up or export drugs. In this context, there is urgent need of application of innovative strategies for identification of novel therapeutic drug targets affecting metabolic pathways essential for survival of the parasites using modern molecular approaches (functional/genomics/ proteomics/bioinformatics). In this review we have discussed existing drugs in use for treatment and outline of emerging approaches in identification and evaluation of potential novel therapeutic targets against trypanosomatids.

Molecular characterization, modeling, in silico analysis of equine pituitary gonadotropin alpha subunit and docking interaction studies with ganirelix.

Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (ß) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist. The equine chorionic gonadotropin (eCG) alpha subunit expressed in pituitary gland was selected, amplified from total RNA, cloned and sequenced. The in silico analyses were made for homology modelling, structural details, epitope identification and chromosomal localization. Molecular docking studies of eCG alpha were undertaken with a drug ganirelix which is used to control ovulation and has antagonistic activity against GnRH. The protein sequence corresponding to selected open reading frame (ORF) was 99-100% similar with domesticated horse, Przewalski's horse, and 92-93% with Burchell's zebra and donkey. Molecular docking studies revealed the possible interaction of eCG alpha with ganirelix. The possible drug-macromolecule interactions were visualized between eCG alpha and ganirelix. The study will provide structural insight into unique sites and an alternate route of gonadotropin suppression applicable to assisted reproductive technologies.

Pathogenicity test of bacterial and fungal fish pathogens in Cirrihinus mrigala infected with EUS disease.

The study was conducted for 8 weeks to determine pathogenic effect of different fish pathogens in Cirrihinus mrigal (C. mrigala) which was infected with EUS disease. The pathogenic organisms (bacteria and fungi) collected from the infected part of the disease fish. Isolation and screening of microbes were carried out with the help of a number of biochemical tests. A total of eight bacterial isolates were obtained from the diseased fish. Out of eight, six bacteria viz., Streptococcus grp Q1, Aeromonas hydrophilla, Shigella spp., Streptococcus faecalis, Cellobiosococcus sciuri, Micrococcus luteus were found to be pathogenic. The fungus, Aphanomyces invadens was also isolated from the diseased fishes. The pathogenicity of disease causing organisms was tested through in vitro and in vivo experiments in different treatments. The result of experiment was found to be significant at level of p < or = 0.05.