The compromise of virtual screening and its impact on drug discovery

Introduction: Docking and structure-based virtual screening (VS) have been standard approaches in structure-based design for over two decades. However, our understanding of the limitations, potential, and strength of these techniques has enhanced, raising expectations.

Areas covered: Based on a survey of reports in the past five years, we assess whether VS: (1) predicts binding poses in agreement with crystallographic data (when available); (2) is a superior screening tool, as often claimed; (3) is successful in identifying chemical scaffolds that can be starting points for subsequent lead optimization cycles. Data shows that knowledge of the target and its chemotypes in postprocessing lead to viable hits in early drug discovery endeavors.

Expert opinion: VS is capable of accurate placements in the pocket for the most part, but does not consistently score screening collections accurately. What matters is capitalization on available resources to get closer to a viable lead or optimizable series. Integration of approaches, subjective hit selection guided by knowledge of the receptor or endogenous ligand, libraries driven by experimental guides, validation studies to identify the best docking/scoring that reproduces experimental findings, constraints regarding receptor–ligand interactions, thoroughly designed methodologies, and predefined cutoff scoring criteria strengthen VS’s position in pharmaceutical research.     

Trace metal toxicity in some food items in three major markets in Ado-Odo/Ota LGA,Ogun State,Nigeria and associated health implications

BackgroundMany of the markets in Nigeria are open, where foodstuffs are laid bare on flat trays and open baskets, directly exposing them to environmental contaminants. This study aimed at determining whether some food items on sale around an industrialized area of Ogun State are contaminated with trace metals.MethodsSeven different food items – Clarias gariepinus (roasted, fresh and smoked) Bos taurus (dried and fresh beef), zobo leaf (Hibiscus sabdariffa) and crayfish (Astacus leptodactylus) were sampled from three major markets, namely: Lusada, Atan and Ota in Ado-Odo/Ota LGA of Ogun State. They were analyzed for Lead, Cadmium, Nickel, Manganese and Zinc using Atomic Absorption Spectroscopy.ResultsCd was not detected in most of the food items across the markets. Pb, Ni and Mn were detected in very high concentrations above the maximum allowable limits by international regulatory agencies. Zn was the only metal that was generally below regulatory limits in food items across the three markets. The Estimated Daily Intake (EDI) and Target Hazard Quotient (THQ) values were generally higher than values acceptable in food.ConclusionSome of the food items consumed in this area are not entirely safe from metal toxicity and this may have serious health consequences.     

Blood lead level and Helicobacter pylori infection in a healthy population: A cross-sectional study

Abstract

The aim of this study was to investigate whether elevated blood lead level (BLL) is a risk factor for Helicobacter pylori infection. Upper gastrointestinal endoscopy was performed on 2,625 subjects who visited a university hospital for general health examination. H. pylori infection was detected using histologic examination with Giemsa staining, and BLLs were measured. The mean BLL was 2.83?±?1.31?μg/dL. The prevalence of H. pylori infection was 27.8%. The BLL was significantly higher in the H. pylori infection-positive group compared to the non-infected group (2.96?±?1.33?μg/dL vs. 2.78?±?1.30?μg/dL, p?<?0.001), which remained significant after adjusting for other confounders. H. pylori infection significantly increased as the BLL increased (OR: 1.143, 95% CI 1.068–1.223). We found a relationship between BLL elevation and H. pylori infection rate.     

Correlation between lead and cadmium concentration and semen quality

There are contrary reports of association of lead and cadmium with the decline in semen quality. This study evaluates whether seminal lead (Pb) and cadmium (Cd) at environmental concentration are associated with altered semen quality. We conducted a study of healthy fertile and infertile men 20–43 years of age attending the Andrology Laboratory of Reproductive Biology Department for semen analysis. The semen analysis was carried out according to the WHO 2010 guidelines. Seminal lead and cadmium were estimated by ICP‐AES. The lead and cadmium values were significantly higher in infertile subjects. A negative association between seminal lead or cadmium concentration and sperm concentration, sperm motility and per cent abnormal spermatozoa was found. This study shows that exposure to Pb (5.29–7.25 μg dl^?1) and cadmium (4.07–5.92 μg dl^?1) might affect semen profile in men. Age, diet, smoking and tobacco chewing habits may have an influence on the increase in exposure to Pb and Cd in the individual subjects.     

Adsorption of organic compounds and hydrophilicity of bismuth,cadmium and antimony electrodes

The adsorption behavior of various organic compounds at bismuth, antimony, cadmium, mercury and other “mercury-like” metals has been discussed. The systematic trends of the influence of the chemical nature of electrode metal and adsorbate to the molecular interaction parameter, a; limiting Gibbs adsorption, Γ_{A, max}; and Gibbs energy of adsorption, ΔG_A⁰, have been analyzed. The ingredients of the total Gibbs energy of organic compounds adsorption have been found. A new more general method for obtaining the metal-water; interaction Gibbs energy has been worked out and used. It was found that the dependence of Gibbs energy of metal-water interaction on the chemical nature of metal and aliphatic organic compound studied is weak. Only in the case of chemically very different metals, for example for Sb and Zn, the difference of Gibbs energy of metal-water interaction values is somewhat higher than the exactness of the determination of the experimental values of Gibbs energy of organic compound adsorption.     

Brugada-type patterns are easily observed in high precordial lead ECGs in collegiate athletes

Background

Displacement of ECG leads can result in unwarranted findings. We assessed the frequency of Brugada-type patterns in athletes when precordial leads were purposely placed upward.

Methods

Four hundred ninety-one collegiate athletes underwent two ECGs: one with standard leads, one with V1 and V2 along the 2nd intercostal space. A positive Brugada-type pattern was defined as ST elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead ECG. A control group was comprised of 181 outpatients.

Results

No Type 1 patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller, and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and were more likely male.

Conclusions

Proper lead positioning is essential to avoid unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male athletes.