Structure based virtual screening of inhibitors for binding at the allosteric site of HCV RNA dependent RNA polymerase

Hepatitis C Virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at a risk of developing significant morbidity and mortality. There is no effective treatment or prevention till date for HCV infection. We describe the computed binding of 10 compounds to the allosteric binding site of RNA dependent RNA polymerase enzyme. These compounds were identified from the ZINC database through virtual screening followed by ADMET evaluation.     

Effect of temperature and concentration on rheological behavior of xanthan-carob mixed gels

The gelation and melting behavior of 1∶1, 1∶3 xanthan-carob mixed gels were evaluated at isothermal and non-isothermal states, as a function of total polymer concentrations of 0.1, 0.5 and 1%. A thermal hysteresis was observed between gelation and melting. The higher the polymer concentration, the higher the melting temperature. The gelation points were determined by three criteria. Depending on the criterion used the gelation temperature was different (52 to 70°C). Pseudoequilibrium modulus and elastic active network chain (EANC) concentration were calculated from the plateau modulus in the frequency spectrum. Temperature dependence of the monomeric friction coefficient was estimated from the relaxation time and EANC. Time-temperature superposition theory was not applicable due to dramatic phase transitions occurring during the gelation of X/C mixture.     

Computer simulated modeling of biomolecular systems.

This paper describes the algorithm of a program used to simulate three dimensional models of molecules. In addition to open ended molecules the program also enables simulation of structures with constraints in the form of cyclic regions or fixed location of particular atoms. Several molecules can be handled in a single run and each molecule can have any number of contraints. Further, any number of conformations can be obtained for each constrained region. The program can be used for research in several areas of molecular biology, e.g., structure determination, conformational analysis and topographic comparisons.     

Studies on germinal effects of quercetin, a naturally occurring flavonoid

Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the most widely occurring flavonoids ingested by man in food. It has been shown to be mutagenic in prokaryotes as well as in in vitro mammalian cell lines. In view of the unavoidability of ingesting it via a normal diet, there is a need to assess the potential genetic risk to man, due to flavonoid ingestion, using whole animal assays. Dominant lethal studies have been carried out in adult Swiss male mice and Wistar male rats to investigate the germinal effects of quercetin. Adult Swiss males were treated with 200, 300 or 400 mg/kg of quercetin dissolved in 60% dimethyl sulfoxide, intraperitoneally. In the rat study, 200 and 300 mg/kg of quercetin were used. Individually caged males were paired with untreated females for a week and six sequential matings were carried out. Two independent experiments in mice and a single experiment in rats constituted the study. Females were evaluated for inducted dominant lethality during the midterm of pregnancy. At 200 mg/kg dose of quercetin, there were no significant differences between control and the test group in pregnancy, total or live implantations in mice or rats during the whole test period that could be attributed to the flavonoid exposure. In mice at 300 and 400 mg/kg of quercetin, there was a profound reduction in fertility of the males during all six matings. The number of total and live implantations also decreased, particularly at the 400 mg/kg dose, although the sample size was too small to be statistically significant. Contrary to this, the rat study did not show any impairment of fertility, nor was there any substantial suppression of total and live implantations at the highest (300 mg/kg) dose tested. There were no significant differences between control and treated groups with regard to the number of dead implantations at any dosage level at any stage of the study in mice and rats. Thus, no post-implantation losses--a reliable measure of dominant lethal mutations--were induced by quercetin in mice or rats. The loss of fertility could be due to germinal cytotoxicity, oligospermia or impairment of fertilizing ability of the treated animals.(ABSTRACT TRUNCATED AT 400 WORDS)