In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease

Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.     

Efficacy and repellency of some essential oils and their blends against larval and adult house flies,Musca domestica L. (Diptera: Muscidae)

House flies are global pests and notoriously difficult to control. Essential oils of vetiver, cinnamon, and lavender and their blends were tested for toxic and repellent effects against larval and adult flies. All of the oils had moderate toxicity for eggs. Mortality of 2^nd instar larvae was 57–78% in dipping assays, 38–100% in contact assays, and 94–100% in treated media. Lavender was less effective (38% mortality) than the others (91–100%) in contact bioassays. Oil blends were not more effective against larvae than individual oils. Vetiver and cinnamon oils were strongly repellent (84 and 78%, respectively) for larvae in treated media. None of the oils were repellent for adult house flies in olfactometer assays, but testing of additional products demonstrated significant repellency for neem oil, p‐menthane‐3,8‐diol (PMD), and vanillin. Contact/fumigant toxicity of vetiver, cinnamon, and lavender oils was 100%, significantly higher than mortality from sunflower oil (67%). Blends of oils were not more effective against adults than the individual oils, but blends diluted with sunflower oil were as effective as the individual oils. Essentials oils of vetiver and cinnamon may have potential for fly management in situations where conventional insecticides cannot be used.     

In Silico Analysis of Usher Encoding Genes in Klebsiella pneumoniae and Characterization of Their Role in Adhesion and Colonization

Chaperone/usher (CU) assembly pathway is used by a wide range of Enterobacteriaceae to assemble adhesive surface structures called pili or fimbriae that play a role in bacteria-host cell interactions. In silico analysis revealed that the genome of Klebsiella pneumoniae LM21 harbors eight chromosomal CU loci belonging to γκп and ϭ clusters. Of these, only two correspond to previously described operons, namely type 1 and type 3-encoding operons. Isogenic usher deletion mutants of K. pneumoniae LM21 were constructed for each locus and their role in adhesion to animal (Intestine 407) and plant (Arabidopsis thaliana) cells, biofilm formation and murine intestinal colonization was investigated. Type 3 pili usher deleted mutant was impaired in all assays, whereas type 1 pili usher deleted mutant only showed attenuation in adhesion to plant cells and in intestinal colonization. The LM21ΔkpjC mutant was impaired in its capacity to adhere to Arabidopsis cells and to colonize the murine intestine, either alone or in co-inoculation experiments. Deletion of LM21kpgC induced a significant decrease in biofilm formation, in adhesion to animal cells and in colonization of the mice intestine. The LM21∆kpaC and LM21∆kpeC mutants were only attenuated in biofilm formation and the adhesion abilities to Arabidopsis cells, respectively. No clear in vitro or in vivo effect was observed for LM21∆kpbC and LM21∆kpdC mutants. The multiplicity of CU loci in K. pneumoniae genome and their specific adhesion pattern probably reflect the ability of the bacteria to adhere to different substrates in its diverse ecological niches.     

Predation risk tradeoffs in prey: effects on energy and behaviour

The complexity of behavioural interactions in predator-prey systems has recently begun to capture trait-effects, or non-lethal effects, of predators on prey via induced behavioural changes. Non-lethal predation effects play crucial roles in shaping population and community dynamics, particularly by inducing changes to foraging, movement and reproductive behaviours of prey. Prey exhibit trade-offs in behaviours while minimizing predation risk. We use a novel evolutionary ecosystem simulation EcoSim to study such behavioural interactions and their effects on prey populations, thereby addressing the need for integrating multiple layers of complexity in behavioural ecology. EcoSim allows complex intra- and inter-specific interactions between behaviourally and genetically unique individuals called predators and prey, as well as complex predator-prey dynamics and coevolution in a tri-trophic and spatially heterogeneous world. We investigated the effects of predation risk on prey energy budgets and fitness. Results revealed that energy budgets, life history traits, allocation of energy to movements and fitness-related actions differed greatly between prey subjected to low-predation risk and high-predation risk. High-predation risk suppressed prey foraging activity, increased total movement and decreased reproduction relative to low-risk. We show that predation risk alone induces behavioural changes in prey which drastically affect population and community dynamics, and when interpreted within the evolutionary context of our simulation indicate that genetic changes accompanying coevolution have long-term effects on prey adaptability to the absence of predators.     

Identification of new protein-protein interactions involving the products of the chromosome- and plasmid-encoded type IV secretion loci of the phytopathogen Xanthomonas axonopodis pv. citri

The recently sequenced genome of the bacterial plant pathogen Xanthomonas axonopodis pv. citri contains two virB gene clusters, one on the chromosome and one on a 64-kb plasmid, each of which codes for a previously uncharacterized type IV secretion system (T4SS). Here we used a yeast two-hybrid assay to identify protein-protein interactions in these two systems. Our results revealed interactions between known T4SS components as well as previously uncharacterized interactions involving hypothetical proteins coded by open reading frames in the two X. axonopodis pv. citri virB loci. Our results indicate that both loci may code for previously unidentified VirB7 proteins, which we show interact with either VirB6 or VirB9 or with a hypothetical protein coded by the same locus. Furthermore, a set of previously uncharacterized Xanthomonas proteins have been found to interact with VirD4, whose gene is adjacent to the chromosomal virB locus. The gene for one member of this family is found within the chromosomal virB locus. All these uncharacterized proteins possess a conserved 120-amino-acid domain in their C termini and may represent a family of cofactors or substrates of the Xanthomonas T4SS.     

A malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites

Membrane skeletons are structural elements that provide mechanical support to the plasma membrane and define cell shape. Here, we identify and characterize a putative protein component of the membrane skeleton of the malaria parasite. The protein, named PbIMC1a, is the structural orthologue of the Toxoplasma gondii inner membrane complex protein 1 (TgIMC1), a component of the membrane skeleton in tachyzoites. Using targeted gene disruption in the rodent malaria species Plasmodium berghei, we show that PbIMC1a is involved in sporozoite development, is necessary for providing normal sporozoite cell shape and mechanical stability, and is essential for sporozoite infectivity in insect and vertebrate hosts. Knockout of PbIMC1a protein expression reduces, but does not abolish, sporozoite gliding locomotion. We identify a family of proteins related to PbIMC1a in Plasmodium and other apicomplexan parasites. These results provide new functional insight in the role of membrane skeletons in apicomplexan parasite biology.     

Expression of platelet-derived growth factor and its receptors in spontaneous canine hemangiosarcoma and cutaneous hemangioma

Hemangiosarcoma (HSA) is a malignant neoplasia of vascular endothelial cells (ECs). Our previous report on the expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors in canine HSA suggested an autocrine/ paracrine mechanism of tumor growth. However, the influence of other angiogenic growth factors in canine HSA was not elucidated; therefore, the expression of platelet-derived growth factor (PDGF) and its receptors was investigated by immunohistochemical analysis. Forty-six canine HSAs and 21 canine cutaneous hemangiomas (HAs) were analyzed. For immunohistochemistry, anti-PDGF-BB, anti-PDGFR-α, and anti-PDGFR-β antibodies were utilized as primary antibodies. Immunoreactivities were scored as strongly positive (>25% positive neoplastic cells), weakly positive (1-25% positive neoplastic cells), and negative if not staining at all. In cutaneous HA, 33.3% and 57.1% of cases were strongly and weakly positive, respectively, and 43.5% and 13.0% of HSAs were strongly and weakly positive for PDGF-BB, respectively. Moreover, 38.1% and 28.6% of cutaneous HAs cases were strongly and weakly positive, respectively, and 23.9% and 4.3% of HSAs cases were strongly and weakly positive, respectively, for PDGFR-α. Thirty-five HSAs cases (76.1%) were strongly positive, and the remaining 11 (23.9%) were weakly positive for PDGFR-β. In contrast, 18 (72.0%) cutaneous HAs were negative, and only 3 cases (12.0%) were weakly positive, for PDGFR-β. The proportion of strongly positive cases of HSAs was significantly higher than that of cutaneous HA for PDGFR-β (P<0.01), while PDGFR-α was highly expressed in cutaneous HA and may be related to pathogenesis of cutaneous HA. Therefore, PDGFR-β may be associated with the malignant nature of canine HSA.     

Global genetic diversity of Aedes aegypti

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co‐occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub‐Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans‐Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations.