The Human Immunodeficiency Virus (HIV) infects approximately 40 million people globally, and one million people die every year from Acquired Immune Deficiency Syndrome (AIDS)-related illnesses. This study examined the interactions between the HIV-1 envelope glycoprotein gp120 and the human lymphocyte receptor integrin α4β7, the putative first long-range receptor for the envelope glycoprotein of the virus in mucosal tissues. Presented data support the claim that the V1 loop is involved in the binding between α4β7 and the HIV-1 envelope glycoprotein through molecular dockings.
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.
The authors use molecular modeling to test analogs of the stearoyl-coenzyme A desaturase 1 (SCD1) inhibitor MF-438 with implications for future development of Parkinson's disease therapeutics.
The Wnt signaling pathway, known to coordinate important aspects of cellular homeostasis ranging from differentiation, proliferation, migration, and much more, is dysregulated in many human diseases. This study demonstrates that aminomethylphosphonic acid, which is the main metabolite found in the common herbicide Glyphosate, is toxic to planaria and capable of binding to canonical Wnt proteins.
In this study, the authors investigate the antibacterial efficacy of penicillin G and its analogs amoxicillin, carbenicillin, piperacillin, cloxacillin, and ampicillin, against four species of bacteria. Results showed that all six penicillin-type antibiotics inhibit Staphylococcus epidermidis, Escherichia coli, and Neisseria sicca with varying degrees of efficacy but exhibited no inhibition against Bacillus cereus. Penicillin G had the greatest broad-spectrum antibacterial activity with a high radius of inhibition against S. epidermidis, E. coli, and N. sicca.
Berberine is a natural quaternary alkaloid that has anti-microbial and anti-cancer effects. This compound can bind to Guanine Quadruplex (G4) DNA secondary complexes to help inhibit cancer cell proliferation. In this study, the authors investigate whether incorporating large aromatic rings helps to stabilize berberine-G4 interactions.
Berberine, a natural product alkaloid, and its analogs have a wide range of medicinal properties, including antibacterial and anticancer effects. Here, the authors explored a library of alkyl or aryl berberine analogs to probe binding to double-stranded and G-quadruplex DNA. They determined that the nature of the substituent, the position of the substituent, and the nucleic acid target affect the free energy of binding of berberine analogs to DNA and G-quadruplex DNA, however berberine analogs did not result in net stabilization of G-quadruplex DNA.
Here, through protein-ligand docking, the authors investigated the effect of the interaction of emodin with serine/threonine kinases, a subclass of kinases that is overexpressed in many cancers, which is implicated in phosphorylation cascades. Through molecular dynamics theyfound that emodin forms favorable interactions with chitosan and chitosan PEG (polyethylene glycol) copolymers, which could aid in loading drugs into nanoparticles (NPs) for targeted delivery to cancerous tissue. Both polymers demonstrated reasonable entrapment efficiencies, which encourages experimental exploration of emodin through targeted drug delivery vehicles and their anticancer activity.
Molecules which bind to proteins that aggregate abnormally in neurodegenerative diseases could be promising drugs for these diseases. In this study, Zhang, Wu, Zhang, and Dang simulate the binding behavior of various molecules to screen for candidates which could be promising candidates for drug development.
Anticholinergics are used in treating asthma, a chronic inflammation of the airways. These drugs block human M1 and M2 muscarinic acetylcholine receptors, inhibiting bronchoconstriction. However, studies have reported complications of anticholinergic usage, such as exacerbated eosinophil production and worsened urinary retention. Modification of known anticholinergics using bioisosteric replacements to increase efficacy could potentially minimize these complications. The present study focuses on identifying viable analogs of anticholinergics to improve binding energy to the receptors compared to current treatment options. Glycopyrrolate (G), ipratropium (IB), and tiotropium bromide (TB) were chosen as parent drugs of interest, due to the presence of common functional groups within the molecules, specifically esters and alcohols. Docking score analysis via AutoDock Vina was used to evaluate the binding energy between drug analogs and the muscarinic acetylcholine receptors. The final results suggest that G-A3, IB-A3, and TB-A1 are the most viable analogs, as binding energy was improved when compared to the parent drug. G-A4, IB-A4, IB-A5, TB-A3, and TB-A4 are also potential candidates, although there were slight regressions in binding energy to both muscarinic receptors for these analogs. By researching the effects of bioisosteric replacements of current anticholinergics, it is evident that there is a potential to provide asthmatics with more effective treatment options.
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