In this study, the authors use high-throughput virtual screening to design and evaluate a set of non-nucleoside reverse transcriptase inhibitors for binding affinity to the protein reverse transcriptase. These studies have important applications toward HIV therapies.

With advancements in machine learning a large data scale, high throughput virtual screening has become a more attractive method for screening drug candidates. This study compared the accuracy of molecular descriptors from two cheminformatics Mordred and PaDEL, software libraries, in characterizing the chemo-structural composition of 53 compounds from the non-nucleoside reverse transcriptase inhibitors (NNRTI) class. The classification model built with the filtered set of descriptors from Mordred was superior to the model using PaDEL descriptors. This approach can accelerate the identification of hit compounds and improve the efficiency of the drug discovery pipeline.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors that bind to the HIV reverse transcriptase and prevent replication. Indolyl aryl sulfones (IAS) and IAS derivatives have been found to be highly effective against mutant strains of HIV-1 reverse transcriptase. Here, we analyzed molecules designed using aryl sulfone scaffolds paired to cyclic compounds as potential NNRTIs through the computational design and docking of 100 novel NNRTI candidates. Moreover, we explored the specific combinations of functional groups and aryl sulfones that resulted in the NNRTI candidates with the strongest binding affinity while testing all compounds for carcinogenicity. We hypothesized that the combination of an IAS scaffold and pyrimidine would produce the compounds with the best binding affinity. Our hypothesis was correct as the series of molecules with an IAS scaffold and pyrimidine exhibited the best average binding affinity. Additionally, this study found 32 molecules designed in this procedure with higher or equal binding affinities to the previously successful IAS derivative 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide when docked to HIV-1 reverse transcriptase.

Chronic alcohol consumption can cause cardiac myopathy, which afflicts about 500,000 Americans annually. Gunturi et al. wanted to understand the effects of alcohol on heart rate and confirm the role of nitric oxide (NO) signaling in heart rate regulation. Using the model organism Daphnia magna, a water crustacean with a large, transparent heart, they found that the heart rate of Daphnia magna was reduced after treatment with alcohol. This depression could be reversed after treatment with inhibitors of NO synthesis and signaling. Their work has important implications for how we understand alcohol-induced effects on heart rate and potential treatments to reverse heart rate depression as a result of alcohol consumption.

Human immunodeficiency virus (HIV), which affects tens of millions of individuals worldwide, can lead to acquired immunodeficiency syndrome (AIDS). While there is currently no cure for HIV, the development of small molecule antiretroviral agents has greatly improved the prognosis of infected individuals, especially in developed countries. Here, the authors employ homology modeling and molecular docking towards the identification of novel rilpivirine analogs that retain high binding affinity to clinically relevant rilpivirine-resistant mutations of the HIV reverse transcriptase enzyme.

Ischemic stroke occurs when blood flow to the brain is interrupted, causing brain damage. This study investigated the effectiveness of different NOX inhibitors as treatments for ischemic stroke in silico. The results help corroborate previous in vivo and in vitro studies in an in silico format, and can be used towards developing drugs to treat ischemic stroke.

Since cancer cells inhibit T-cell activity, the authors investigated a method to reverse T-cell disfunction with gene therapy, so that the T-cells would become effective once again in fighting cancer cells. They used the inhibition of proprotein convertases (PCSK1) in T cells and programmed death-ligand 1 (CD274) in cancer cells. They observed the recovery of IL-2 expression in Jurkat cells, with increased recovery noted in a co-culture sample. This study suggests a novel strategy to reactivate T cells.

Ant invasion causes damage exceeding $5 billion annually in North America. In this study, Ambati and Duvvuri aim to identify natural products with ant-repelling properties using a custom ring apparatus designed to quantify ant-repellence. They report that cinnamon and lemon were the most effective ant repellents of the tested products. These data suggest that compounds found in non-toxic household products, such as cinnamon oil and lemon juice, could be used in low-dose combinations as potent, effective, eco-friendly, and safe ant repellents.

Here, based on identification of iron deficiencies of a majority of people around the world, the authors sought to understand how the two main forms of dietary iron, heme and non-heme, affect the bacteria found in the human gut. by using a cell plate study, they found that bacterial growth increased with increasing concentration os either form of iron, up until the point where the high iron content resulted in cytotoxicity. They suggest this evidence points to the potential dangers of overconsumption of iron.

Diabetes is a serious worldwide epidemic that affects a growing portion of the population. While the most common method for testing blood glucose levels involves finger pricking, it is painful and inconvenient for patients. The authors test a non-invasive method to measure glucose levels from diabetic patients, and investigate whether the method is clinically accurate and universally applicable.