Additional file 2: Table S2. of In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Average Numerical Grade of Leukocytes in the Vaginal Lamina Propria during Diestrus by Group. The number of female mice in diestrus is listed according to average leukocyte grade by treatment group. (DOC 43 kb

Additional file 4: Table S4. of In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Average Percent Viability of Cervical Explant Cells with Increasing Concentration of CuPcS. Toxicity as measured using MTT assay is presented for cervical explant cells over seven days of exposure to CuPcS. Percent viability was determined as a function of optical density compared with controls. Concentrations were tested in quadruplicate. (DOC 25 kb

Additional file 1: Table S1. of In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Number of Animals by Estrous Phase and Treatment Group. The number of female mice in each treatment group is subdivided based on stage of estrus. (DOC 28 kb

Additional file 3: Table S3. of In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Average Numerical Grade of Leukocytes in the Vaginal Lamina Propria during Proestrus by Group. The number of female mice in proestrus is listed according to average leukocyte grade by treatment group. (DOC 44 kb

Discovery of a Novel and Potent Class of F. tularensis Enoyl-Reductase (FabI) Inhibitors by Molecular Shape and Electrostatic Matching

Enoyl-acyl carrier protein (ACP) reductase, FabI, is a key enzyme in the bacterial fatty acid biosynthesis pathway (FAS II). FabI is an NADH-dependent oxidoreductase that acts to reduce enoyl-ACP substrates in a final step of the pathway. The absence of this enzyme in humans makes it an attractive target for the development of new antibacterial agents. FabI is known to be unresponsive to structure-based design efforts due to a high degree of induced fit and a mobile flexible loop encompassing the active site. Here we discuss the development, validation, and careful application of a ligand-based virtual screen used for the identification of novel inhibitors of the Francisella tularensis FabI target. In this study, four known classes of FabI inhibitors were used as templates for virtual screens that involved molecular shape and electrostatic matching. The program ROCS was used to search a high-throughput screening library for compounds that matched any of the four molecular shape queries. Matching compounds were further refined using the program EON, which compares and scores compounds by matching electrostatic properties. Using these techniques, 50 compounds were selected, ordered, and tested. The tested compounds possessed novel chemical scaffolds when compared to the input query compounds. Several hits with low micromolar activity were identified and follow-up scaffold-based searches resulted in the identification of a lead series with submicromolar enzyme inhibition, high ligand efficiency, and a novel scaffold. Additionally, one of the most active compounds showed promising whole-cell antibacterial activity against several Gram-positive and Gram-negative species, including the target pathogen. The results of a preliminary structure–activity relationship analysis are presented

Cytokines and sTNFr1 endocervical expression.

<p>Data represents median and interquartile range. TV = <i>Trichomonas vaginalis</i>. P values are the result of Mann-Whitney test.</p

Baseline characteristics of ESN by <i>T</i>. <i>vaginalis</i> status.

<p>ESN = female sex workers, TV = <i>T</i>. <i>vaginalis</i>, IUD = intrauterine device, tubal = tubal ligation, STI = sexually transmitted infection; Values represent N (%) unless otherwise noted.</p><p>Baseline characteristics of ESN by <i>T</i>. <i>vaginalis</i> status.</p

Gating strategy for mononuclear cell expression.

<p>Dead cells were excluded with a viability stain before gating on CD45+ cells. CD45+ cells were further analyzed for CD3+ and CD14+ expression. CD45+CD3+ cells were gated on CD4+ or CD8+ before HLA-DR/CD38 quadrant gating as well as CCR5 co-receptor expression. CD45+CD14+ cells were also analyzed for CCR5 expression.</p