In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaporthe oryzae.

Magnaporthe oryzae causes destructive blast disease in more than 50 species of the major cereal crops rice, wheat and maize and destroys food of millions of people worldwide. Application of synthetic chemical fungicides are environmentally hazardous and unreliable in controlling M. oryzae. Conversely, naturally occurring biofungicides with multiple modes of actions are needed to be discovered for combatting the blast fungus. To find the effective biofungicides, we performed molecular docking study of some potential antifungal natural compounds targeting two proteins including a single-stranded DNA binding protein MoSub1 (4AGH), and an effector protein AVR-Pik (5E9G) of M. oryzae that regulates transcription in fungus and/or suppresses the host cell immunity. The thirty-nine natural compounds previously shown to inhibit M. oryzae growth and reproduction were put under molecular docking against these two proteins followed by simulation, free energy, and interaction analysis of protein-ligand complexes. The virtual screening revealed that two alkaloidal metabolites, camptothecin and GKK1032A2 showed excellent binding energy with any of these target proteins compared to reference commercial fungicides, azoxystrobin and strobilurin. Of the detected compounds, GKK1032A2 bound to both target proteins of M. oryzae. Both compounds showed excellent bioactivity scores as compared to the reference fungicides. Results of our computational biological study suggest that both camptothecin and GKK1032A2 are potential fungicides that could also be considered as lead compounds to design novel fungicides against the blast fungus. Furthermore, the GKK1032A2 acted as a multi-site mode of action fungicide against M. oryzae.

Drug Repurposing and Systems Biology approaches of Enzastaurin can target potential biomarkers and critical pathways in Colorectal Cancer.

Colorectal cancer (CRC) is a severe health concern that results from a cocktail of genetic, epigenetic, and environmental abnormalities. Because it is the second most lethal malignancy in the world and the third-most common malignant tumor, but the treatment is unavailable. The goal of the current study was to use bioinformatics and systems biology techniques to determine the pharmacological mechanism underlying putative important genes and linked pathways in early-onset CRC. Computer-aided methods were used to uncover similar biological targets and signaling pathways associated with CRC, along with bioinformatics and network pharmacology techniques to assess the effects of enzastaurin on CRC. The KEGG and gene ontology (GO) pathway analysis revealed several significant pathways including in positive regulation of protein phosphorylation, negative regulation of the apoptotic process, nucleus, nucleoplasm, protein tyrosine kinase activity, PI3K-Akt signaling pathway, pathways in cancer, focal adhesion, HIF-1 signaling pathway, and Rap1 signaling pathway. Later, the hub protein module identified from the protein-protein interactions (PPIs) network, molecular docking and molecular dynamics simulation represented that enzastaurin showed strong binding interaction with two hub proteins including CASP3 (-8.6 kcal/mol), and MCL1 (-8.6 kcal/mol), which were strongly implicated in CRC management than other the five hub proteins. Moreover, the pharmacokinetic features of enzastaurin revealed that it is an effective therapeutic agent with minimal adverse effects. Enzastaurin may inhibit the potential biological targets that are thought to be responsible for the advancement of CRC and this study suggests a potential novel therapeutic target for CRC.

Extensive immunoinformatics study for the prediction of novel peptide-based epitope vaccine with docking confirmation against envelope protein of Chikungunya virus: a computational biology approach.

Chikungunya virus (CHIKV) instigating Chikungunya fever is a global infective menace resulting in high fever, weakened joint-muscle pain, and brain inflammation. Inaccessibility and unavailability of effective drugs have led us to an uncertain arena when it comes to providing proper medical treatment to the affected people. In this study, authentic encroachment has been made concerning the peptide-based epitope vaccine designing against CHIKV. A Proteome-wide search was performed to locate a conserved portion among the accessible viral outer membrane proteins which showcase a remarkable immune response using specific immunoinformatics and docking simulation tools. Primarily, the most probable immunogenic envelope glycoproteins E1 and E2 were identified from the UniProt database depending on their antigenicity scores. Subsequently, we selected two distinctive sequences "SEDVYANTQLVLQRP" and "IMLLYPDHPTLLSYR" in both E1 and E2 glycoproteins respectively. These two sequences identified as the most potent T and B cell epitope-based peptides as they interacted with 6 and 7 HLA-I and 5 HLA-II molecules with an extremely low IC50 score that was verified by molecular docking. Moreover, the sequences possess no allergenicity and are certainly located outside the transmembrane region. In addition, the sequences exhibited 88.46% and 100.00% Conservancy, covering high population coverage of 89.49% to 94.74% and 60.51% to 88.87% respectively in endemic countries. The identified peptide SEDVYANTQLVLQRP and IMLLYPDHPTLLSYR can be utilized next for the development of peptide-based epitope vaccine contrary to CHIKV, so further documentations and experimentations like Antigen testing, Antigen production, Clinical trials are needed to prove the validity of it. Communicated by Ramaswamy H. Sarma.

Arsenic hampered embryonic development: An in vivo study using local Bangladeshi Danio rerio model.

Zebrafish (Danio rerio) has appeared as a valuable and popular model species to study the developmental and toxicological impact of environmental pollutants. To get insights on the toxicological effect of arsenic on early embryonic development, a controlled breeding of local Bangladeshi zebrafish followed by comprehensive microscopic analysis was conducted to study the embryonic development after exposure to different concentrations of arsenic ranges from 4-120 h post-fertilization. Zebrafish embryos exposed to 2 mM of arsenic displayed distinguishable developmental delay compared to control. At three days post-fertilization, a distinct phenotype appears in arsenic-treated embryos, which can be characterized by dechorionated embryos, larger egg mass, pericardial edema, abnormal heart rate, and abnormal head development. Remarkably, the death rate of the arsenic-treated embryos was significantly higher compared to control. Collectively, these findings indicate that exposure to arsenic may result in abnormal embryonic development. These results suggest for proper management of the pregnant mother in the arsenic-exposed area, and may also explain the incidence of increased miscarriage/abortion rate in arsenic water drinking pregnant mother.

Prevalence, Antimicrobial Resistance, and Pathogenic Potential of Enterotoxigenic and Enteropathogenic Escherichia coli Associated with Acute Diarrheal Patients in Tangail, Bangladesh.

In this study, the prevalence and antimicrobial resistance of enterotoxigenic Escherichia coli (ETEC) and enteropathogenic Escherichia coli (EPEC) were investigated. Altogether 100 stool samples were collected from diarrheal patients attending the Sheikh Hasina Medical College and Hospital, Tangail, Bangladesh, during the period from March 1 to May 30, 2018. In vivo pathogenic potential of ETEC and EPEC using a Caenorhabditis elegans infection model was investigated. Among 100 diarrheal patients, 31% were positive for both ETEC and EPEC strains, 23% were lt positive for ETEC strains, and 8% were bfpA positive for EPEC strains. It was detected that 82.60%, 65.21%, 73.91%, 78.26%, 47.82%, 60.86%, and 47.82% of ETEC strains were resistant to amoxicillin-clavulanic acid (AMC), tetracycline (TE), nalidixic acid (NA), azithromycin, ciprofloxacin, ampicillin (AMP), and erythromycin (E), respectively. Whereas it was detected that 87.5% strains were resistant to AMC, AMP, and E, 75% were resistant to TE and NA, respectively. Both strains developed multidrug resistance to commonly prescribed antibiotics. EPEC showed higher pathogenicity than ETEC as 67.75% and 60% of C. elegans died after 18 h postinfection with EPEC and ETEC, respectively. The high rate of antimicrobial resistance of EPEC and ETEC highlights the necessity for the prudent use of antimicrobials in Bangladesh.

Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes.

The cold shock domain is one of the most highly conserved motifs between bacteria and higher eukaryotes. Y-box-binding proteins represent a subfamily of cold shock domain proteins with pleiotropic functions, ranging from transcription in the nucleus to translation in the cytoplasm. These proteins have been investigated in all major model organisms except Caenorhabditis elegans. In this study, we set out to fill this gap and present a functional characterization of CEYs, the C. elegans Y-box-binding proteins. We find that, similar to other organisms, CEYs are essential for proper gametogenesis. However, we also report a novel function of these proteins in the formation of large polysomes in the soma. In the absence of the somatic CEYs, polysomes are dramatically reduced with a simultaneous increase in monosomes and disomes, which, unexpectedly, has no obvious impact on animal biology. Because transcripts that are enriched in polysomes in wild-type animals tend to be less abundant in the absence of CEYs, our findings suggest that large polysomes might depend on transcript stabilization mediated by CEY proteins.