Identification of promising anti-DNA gyrase antibacterial compounds using design, molecular docking and molecular dynamics studies.

The rapidly increasing rate of antibiotic resistance is of great concern. Approximately two million deaths result annually from bacterial infections worldwide. Therefore, there is a paramount requirement to develop innovative and novel antibacterial agents with new mechanisms of action and activity against resistant bacterial strains.

Pharmacoinformatics-based identification of chemically active molecules against Ebola virus.

Ebola is a dangerous virus transmitted by animals and humans and to date there is no curable agent for such a deadly infectious disease. In this study, pharmacoinformatics-based methods were adopted to find effective novel chemical entities against Ebola virus. A well predictive and statistical robust pharmacophore model was developed from known Ebola virus inhibitors collected from the literature.

Molecular dynamics and combined docking studies for the identification of Zaire ebola virus inhibitors.

Ebola virus (EBOV) is a lethal human pathogen with a risk of global spread of its zoonotic infections, and specifically has the highest fatality rate amongst other species. There is a need for continuous effort towards having therapies, as a single licensed treatment to neutralize the EBOV is yet to come into reality. This present study virtually screened the MCULE database containing almost 36 million compounds against the structure of a Zaire Ebola viral protein (VP) 35 and a consensus scoring of both MCULE and CLCDDW docking programs remarked five compounds as potential hits.

β-secretase inhibitors for Alzheimer's disease: identification using pharmacoinformatics.

In this study we searched for potential β-site amyloid precursor protein cleaving enzyme1 (BACE1) inhibitors using pharmacoinformatics. A large dataset containing 7155 known BACE1 inhibitors was evaluated for pharmacophore model generation. The final model (R = 0.

A small proportion of community-associated methicillin-resistant Staphylococcus aureus bacteraemia, compared to healthcare-associated cases, in two South African provinces.

We compared the proportion of cases of community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus (CA-MRSA and HA-MRSA, respectively) bacteraemia among patients at five hospitals in the Gauteng and Western Cape provinces in South Africa and described the molecular characteristics and antimicrobial susceptibility trends. This was a cross-sectional study using data collected by enhanced surveillance for S. aureus bacteraemia.

Demand management by electronic gatekeeping of test requests does not influence requesting behaviour or save costs dramatically.

Background Healthcare budgets face constraints, and laboratories have developed strategies to adapt to the concomitant increase in workload. Some of the tests (7.4%) may be attributed to unnecessary repeat testing.

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB.

Diabetes mellitus caused by mutations in human insulin: analysis of impaired receptor binding of insulins Wakayama, Los Angeles and Chicago using pharmacoinformatics.

Several naturally occuring mutations in the human insulin gene are associated with diabetes mellitus. The three known mutant molecules, Wakayama, Los Angeles and Chicago were evaluated using molecular docking and molecular dynamics (MD) to analyse mechanisms of deprived binding affinity for insulin receptor (IR). Insulin Wakayama, is a variant in which valine at position A3 is substituted by leucine, while in insulin Los Angeles and Chicago, phenylalanine at positions B24 and B25 is replaced by serine and leucine, respectively.

Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies.

Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease which is a collection of symptoms and infections caused by a retrovirus, human immunodeficiency virus (HIV). There is currently no curative treatment and therapy is reliant on the use of existing anti-retroviral drugs. Pharmacoinformatics approaches have already proven their pivotal role in the pharmaceutical industry for lead identification and optimization.

Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa: Epidemiological investigation and measures to prevent further transmission.

Background: Hospital-acquired hepatitis B virus (HBV) infection has been well described and continues to occur worldwide. Recent nosocomial outbreaks have been linked to unsafe injection practices, use of multi-dose vials, and poor staff compliance with standard precautions. This report describes a nosocomial outbreak that occurred in a pediatric hematology and oncology unit of a large academic hospital, the epidemiological investigation of the outbreak, and preventive measures implemented to limit further in-hospital transmission.

Exploration of the structural requirements of HIV-protease inhibitors using pharmacophore, virtual screening and molecular docking approaches for lead identification.

Pharmacoinformatics approaches are widely used in the field of drug discovery as it saves time, investment and animal sacrifice. In the present study, pharmacore-based virtual screening was adopted to identify potential HIV-protease ligands as anti-HIV agents. Pharmacophore is the 3D orientation and spatial arrangement of functional groups that are critical for binding at the active site cavity.

Evaluation of the utility of serum prolidase as a marker for liver fibrosis.

Background: Liver dysfunction is common and often unrecognized. Liver biopsy is the gold standard in the assessment of liver fibrosis, but has disadvantages. We assessed the diagnostic accuracy of serum prolidase enzyme activity (SPA) in predicting the presence and degree of liver fibrosis, as compared with liver biopsy.

Recent developments in hiv treatment and their dissemination in poor countries.

As the world enters the fourth decade of the HIV/AIDS epidemic a number of new drugs have been developed that address current challenges with antiretroviral therapy (ART), such as pill burden, toxicity and drug-resistance. These new agents have not only been developed from established drug-classes, namely nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), but also include innovative ways of suppressing viral replication. Intergrase inhibitors and chemokine receptor blockers have been developed which, combined with NRTIs, NNRTIs and PIs, comprise highly active antiretroviral therapy regimens able to tackle all aspects of the HIV life cycle with minimal toxicity.

Circulating cytokine profiles and their relationships with autoantibodies, acute phase reactants, and disease activity in patients with rheumatoid arthritis.

Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines.

Integrons and beta-lactamases--a novel perspective on resistance.

The understanding of microbial resistance to the beta-lactam class of antibiotics in the form of beta-lactamases has come a long way since the early discoveries of narrow-spectrum penicillinases. Integron-borne beta-lactamases co-occurring with a wide array of non-beta-lactam resistance genes, particularly pose an increasing threat to the nosocomial environment, giving rise to multi-drug resistant microbes with complex resistance patterns. Selection of potent beta-lactamases through the use of non-beta-lactam agents may be possible through integron-mediated resistance.