BACKGROUND P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in comb...

Inhibitors of mammalian multidrug efflux, such as the plant alkaloid reserpine, are also active in potentiating antibiotic activity by inhibiting bacterial efflux. Based on this precedent, two novel mammalian multiple drug resistance inhibitors, biricodar (VX-710) and timcodar (VX-853), were evaluated for activity in a variety of bacteria. Both VX-710 and VX-853 potentiated the activity of ethi...

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for...

Field portable gas chromatography-mass spectrometry, GC-MS, have been established as the ‘gold standard’ of chemical identification and quantification for threats however several warfare agents shown to evade required detection limits. This work demonstrates derivatization O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) N,N-diethyl-2-[methyl(2-methylpropoxy)phosphoryl]sulfanylet...

The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. VX-950, a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is currently in clinical development for the treatment of hepatitis C. In this report, we de...

Drought stress is a common environmental factor that constrains plants from expressing their ecophysiological potential, disrupting various physiological and biochemical processes. Hence, the objective of this work was to evaluate growth, development photosynthetic performance under drought in vegetative phenological stage soybean two lineages with potential difference tolerance abiotic stress,...

We quantify the adsorption of organophosphate venomous agent X (VX) on clean and hydroxylated (101) surfaces anatase titanium dioxide (TiO2) with density functional theory (DFT) calculations. Our results show that surface occurs through VX phosphoryl oxygen (OP) site involves formation a Ti···OP dative bond. Steric effects inhibit nitrogen sulfur sites by Ti···N Ti···S bonds. On surface, simila...

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygou...

The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leads to deletion of the phenylalanine at position 508 (ΔF508) in the CFTR protein and causes multiple folding and functional defects. Contrary to large-scale efforts by industry and academia, no significant therapeutic benefit has been achieved with a single "corrector". Therefore, investigations co...

Reactions of VX in concrete have been studied in situ using solid state P NMR. The size of VX drops deposited on concrete affect the natural degradation rate, with 4 μL drops reacting faster than 0.2 μL drops. Water added to concrete samples containing sorbed VX to mimic precipitation and/or a potential decontamination strategy resulted in the desorption of copious amounts of VX into the water ...