Haemo- and endoparasites of indigenous chickens reared in Gwagwalada Area Council, Abuja, Nigeria

Poultry production as one of the major sources of protein in Nigeria is constrained by parasitic diseases including haemo- and gastrointestinal (GI) parasites. The haemo- and endoparasites of indigenous chickens reared in Gwagwalada market, Gwagwalada Area Council, Abuja, Nigeria were studied. Blood and fecal samples were collected from 108 chickens (Gallus gallus domesticus) between April­August, 2017. Thin blood smear, and floatation and sedimentation techniques were used for the blood and fecal samples, respectively. Of the 108 local chickens examined, 49 were males, while 59 were females. Overall, female chickens had higher infection rate with haemoparasites (53.1%) that males (46.9%). The blood parasites found mostly were Plasmodium spp., with a prevalence 54.6%, occurring in both male and female chickens examined. It was further revealed that endoparasites infected 60.8% of the female local chicken and 39.2% of the male. The mostly occured Ascaridia spp. with prevalence 35.2%; the least was Strongyloides avium (0.9%). Also, Eimeria spp. occysts were found in 8 (7.4%) of the chickens. This study provides basic information on the haemo- and endoparasites constantly infecting local breed of chickens reared in Gwagwalada Area Council, FCT- Abuja.

Membrane-Bound Transcription Factor Site-1 Protease in PF429242 Bound State: Computational Kinetics and Dynamics of Reversible Binding.

Membrane-bound transcription factor site-1 protease (S1P) is an emerging clinical target due to its roles in lipogenesis, lysosomal biogenesis, unfolded protein response and viral glycoprotein processing. In this study, homology model of S1P was created in order to understand the structural basis for S1P inhibition by PF429242 using molecular docking, molecular dynamics simulation and in silico kinetics studies. PF429242 was docked (GlideScorePF429242=-5.20 kcal/mol) into the catalytic triad (D218, H249 and S414) and validated (R2=0.5686). The reversible binding kinetic parameter (Koff/Kon) was estimated at=7.28E-03 M with fully bound and apo-states interspersed by 3 transient ligand-bound states with unique binding signatures; water plays a major role in PF429242 dissociation from the catalytic site. Communication between key catalytic triad residues is altered in the presence of PF429242. In apo-S1P state, S414-S307/V216-D218 is the preferred route but in PF429242-bound state, S414-S417/V216-D218 is preferred. Communication between S414 and H249 is also shortened in PF429242 bound state; here, only L410 is required unlike apo-state, which requires P418, V256 and F252. Ligand binding did not alter the communication route between S414 and H249 as both recruited D244 and G220. In conclusion, PF429242 binds tightly but reversible to S1P and the details of this interaction has been presented to guide future efforts at developing novel inhibitors. Site-1-protease; PF429242; Kon/Koff; Network analysis.

T-705-modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA-binding pocket.

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA-approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is an emerging alternative drug with proven anti-Lassa virus activity in experimental model. One of the mechanisms of action is its incorporation into nascent single-strand RNA (ssRNA) which forms complex with Lassa nucleoprotein (LASV-NP). Here, using molecular dynamics simulation, the structural and electrostatics changes associated with LASV-NP-ssRNA complex have been studied when none, one, or four of its bases has been substituted with T-705. The results demonstrated that glycosidic torsion angle χ (O4'-C1'-N1-C2) rotated from high-anti- (-110° and -60°) to the syn- conformation (+30) with increased T-705 substitution. Similarly, increased T-705 substitution resulted in increased splaying (55°-70°), loss of ssRNA-LASV-NP H-bond interaction, increased water influx into the ssRNA-binding pocket, and decreased electrostatic potentials of ssRNA pocket. Furthermore, strong positively correlated motion observed between α6 residues (aa: 128-145) and its contact ssRNA bases (5-7) is weakened in Apo biosystem and transitioned into anticorrelated motions in ssRNA-bound LASV-NP biosystem. Finally, LASV genome may become more accessible to cellular ribonuclease access with T-705 incorporation due to loss of NP interaction.