Screening of novel alkaloid inhibitors for vascular endothelial growth factor in cancer cells: an integrated computational approach.

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1).

Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10-15 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324-349 and 252-268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11-19, 163-171 and 233-241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.

Is Childhood Overweight/Obesity Perceived as a Health Problem by Mothers of Preschool Aged Children in Bangladesh? A Community Level Cross-Sectional Study.

Childhood obesity is rapidly rising in many developing countries such as Bangladesh; however, the factors responsible for this increase are not well understood. Being the primary caregivers of children, particularly in developing countries, maternal perceptions and knowledge could be important factors influencing the weight status of children. This study aimed to assess maternal perceptions of childhood obesity and associated socio-demographic factors in Bangladesh. A cross-sectional study using stratified random sampling was conducted among 585 mothers whose children aged 4 to 7 years attended preschools in a district town. Body Mass Index of the children was calculated and weight status categorized according to the Centers for Disease Control (CDC) criteria. Maternal perceptions were assessed using a self- or interviewer-administered questionnaire. Multinomial logistic regression was used to obtain crude and adjusted odds ratios. Fourteen percent of children were overweight or obese and approximately 30% were underweight. Only 3.1% of children were perceived as overweight/obese by their mothers. Over one-third (35%) of mothers perceived that childhood overweight/obesity could be a health problem and over two-thirds (68.6%) were not aware of any health consequences of childhood obesity. Maternal perceptions were significantly associated with maternal education, family income, and weight status of the child but were not associated with the sex of the child. We have identified knowledge gaps regarding maternal perception of childhood obesity and its contributing factors in a developing country. These findings can be used to develop and test parent-focused educational interventions for preventing childhood obesity in Bangladesh.

In silico structure analysis and epitope prediction of E3 CR1-beta protein of Human Adenovirus E for vaccine design.

BACKGROUND: Human Adenoviruses are divided into 7 species of Human Adenovirus A to G based on DNA genome homology. The Human Adenovirus E (HAdVs-E) genome is a linear, double-stranded DNA containing 38 protein-coding genes. Wild-type adenoviruses type E, are linked to a number of slight illnesses. The most important part of HAdVs-E is E3 CR1-beta protein which controls the host immune response and viral attachment. METHOD: We use numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for construction of 3D model and epitope prediction for HAdVs-E. RESULTS: The 3D structure of E3 CR1-beta protein was generated and total of ten antigenic B cell epitopes, 6 MHC class I and 11 MHC class II binding peptides were predicted. CONCLUSION: The study was carried out to predict antigenic determinants/epitopes of the E3 CR1-beta protein of Human Adenovirus E along with the 3D protein modeling. The study revealed potential T-cell and B-cell epitopes that can raise the desired immune response against E3 CR1-beta protein and useful in developing effective vaccines against HAdVs-E.

Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach.

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

In Silico Structural and Functional Annotation of Hypothetical Proteins of Vibrio cholerae O139.

In developing countries threat of cholera is a significant health concern whenever water purification and sewage disposal systems are inadequate. Vibrio cholerae is one of the responsible bacteria involved in cholera disease. The complete genome sequence of V. cholerae deciphers the presence of various genes and hypothetical proteins whose function are not yet understood. Hence analyzing and annotating the structure and function of hypothetical proteins is important for understanding the V. cholerae. V. cholerae O139 is the most common and pathogenic bacterial strain among various V. cholerae strains. In this study sequence of six hypothetical proteins of V. cholerae O139 has been annotated from NCBI. Various computational tools and databases have been used to determine domain family, protein-protein interaction, solubility of protein, ligand binding sites etc. The three dimensional structure of two proteins were modeled and their ligand binding sites were identified. We have found domains and families of only one protein. The analysis revealed that these proteins might have antibiotic resistance activity, DNA breaking-rejoining activity, integrase enzyme activity, restriction endonuclease, etc. Structural prediction of these proteins and detection of binding sites from this study would indicate a potential target aiding docking studies for therapeutic designing against cholera.

A Systematic Study on Structure and Function of ATPase of Wuchereria bancrofti.

BACKGROUND: Analyzing the structures and functions of different proteins of Wuchereria bancrofti is very important because till date no effective drug or vaccine has been discovered to treat lymphatic filariasis (LF). ATPase is one of the most important proteins of Wuchereria bancrofti. Adenosine triphosphate (ATP) converts into adenosine diphosphate (ADP) and a free phosphate ion by the action of these ATPase enzymes. Energy releases from these dephosphorylation reactions drive the other chemical reactions in the cell. MATERIALS AND METHODS: In this study we worked on the protein ATPase of Wuchereria bancrofti which has been annotated from National Center for Biotechnology Information (NCBI). Various computational tools and databases have been used to determine the various characteristics of that enzyme such as physiochemical properties, secondary structure, three-dimensional (3D) structure, conserved domain, epitope, and their molecular evolutionary relationship. RESULT: Subcellular localization of ATPase was identified and we have found that 55.5% are localized in the cytoplasm. Secondary and 3D structure of this protein was also predicted. Both structure and function analysis of ATPase of Wuchereria bancrofti showed unique nonhomologous epitope sites and nonhomologous antigenicity sites. Moreover, it resulted in 15 ligand drug-binding sites in its tertiary structure. CONCLUSION: Structure prediction of these proteins and detection of binding sites and antigenicity sites from this study would indicate a potential target aiding docking studies for therapeutic designing against filariasis.