It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms and quality of life.Although rotavirus infection is usually acute and self-limiting, it can cause chronic infection with severe diseases in immunocompromised patients, including organ transplantation recipients and cancer patients irrespective of pediatric or adult patients. Since no approved medication against rotavirus infection is available, this study screened a library of safe-in-man broad-spectrum antivirals. We identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of rotavirus infection. We confirmed this effect in 2D cell cultures and 3D cultured human intestinal organoids with both laboratory-adapted rotavirus strains and five clinical isolates. Supplementation of UTP or uridine largely abolished the anti-rotavirus activity of gemcitabine, suggesting its function through inhibition of pyrimidine biosynthesis pathway. Our results support repositioning of gemcitabine for treating rotavirus infection, especially for infected cancer patients.How protein domain structure changes in response to mutations is not well understood. Some mutations change the structure drastically, while most only result in small changes. To gain an understanding of this, we decompose the relationship between changes in domain sequence and structure using machine learning. We select pairs of evolutionarily related domains with a broad range of evolutionary distances. In contrast to earlier studies, we do not find a strictly linear relationship between sequence and structural changes. We train a random forest regressor that predicts the structural similarity between pairs with an average accuracy of 0.029 lDDT ( local Distance Difference Test) score, and a correlation coefficient of 0.92. Decomposing the feature importance shows that the domain length, or analogously, size is the most important feature. Our model enables assessing deviations in relative structural response, and thus prediction of evolutionary trajectories, in protein domains across evolution.Chronic infection with the hepatitis B virus (HBV) remains a significant worldwide medical problem. While diseases caused by HIV infection, tuberculosis and malaria are on the decline, new cases of chronic hepatitis B are on the rise. Because often fatal complications of cirrhosis and hepatocellular carcinoma are associated with chronic hepatitis B, the need for a cure is as urgent as ever. Currently licensed therapeutics fail to eradicate the virus and this is attributable to persistence of the viral replication intermediate comprising covalently closed circular DNA (cccDNA). Elimination or inactivation of the viral cccDNA is thus a goal of research aimed at hepatitis B cure. The ability to engineer nucleases that are capable of specific cleavage of a DNA sequence now provides the means to disable cccDNA permanently. The scientific literature is replete with many examples of using designer zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and RNA-guided endonucleases (RGENs) to inactivate HBV. However, important concerns about safety, dose control and efficient delivery need to be addressed before the technology is employed in a clinical setting. Use of in vitro transcribed mRNA to express therapeutic gene editors goes some way to overcoming these concerns. The labile nature of RNA limits off-target effects and enables dose control. Compatibility with hepatotropic non-viral vectors is convenient for the large scale preparation that will be required for advancing gene editing as a mode of curing chronic hepatitis B.Derangements in triglyceride and cholesterol metabolism (dyslipidemia) are major risk factors for the development of cardiovascular diseases in obese and type-2 diabetic (T2D) patients. An emerging class of glucagon-like peptide-1 (GLP-1) analogues and next generation peptide dual-agonists such as GLP-1/glucagon or GLP-1/GIP could provide effective therapeutic options for T2D patients. In addition to their role in glucose and energy homeostasis, GLP-1, GIP and glucagon serve as regulators of lipid metabolism. This review summarizes the current knowledge in GLP-1, glucagon and GIP effects on lipid and lipoprotein metabolism and frames the emerging therapeutic benefits of GLP-1 analogs and GLP-1-based multiagonists as add-on treatment options for diabetes associated dyslipidemia.The anti-malarial drug Chloroquine (CQ) and its derivative hydroxychloroquine have shown antiviral activities in vitro against many viruses, including coronaviruses, dengue virus and the biosafety level 4 Nipah and Hendra paramyxoviruses. The in vivo efficacy of CQ in the treatment of COVID-19 is currently a matter of debate. CQ is a lysosomotrophic compound that accumulates in lysosomes, as well as in food vacuoles of Plasmodium falciparum. In the treatment of malaria, CQ impairs the digestion and growth of the parasite by increasing the pH of the food vacuole. Similarly, it is assumed that the antiviral effects of CQ results from the increase of lysosome pH and the inhibition of acidic proteases involved in the maturation of virus fusion protein. CQ has however other effects, among which phospholipidosis, characterized by the accumulation of multivesicular bodies within the cell. https://www.selleckchem.com/products/Aloxistatin.html The increase in phospholipid species particularly concerns bis(monoacylglycero)phosphate (BMP), a specific lipid of late endosomes involved in vesicular trafficking and pH-dependent vesicle budding. It was shown previously that drugs like progesterone, the cationic amphiphile U18666A and the phospholipase inhibitor methyl arachidonyl fluoro phosphonate (MAFP) induce the accumulation of BMP in THP-1 cells and decrease cell infection by human immunodeficiency virus. HIV viral particles were found to be retained into large endosomal-type vesicles, preventing virus spreading. Since BMP was also reported to favour virus entry through hijacking of the endocytic pathway, we propose here that BMP could play a dual role in viral infection, with its antiviral effects triggered by lysosomotropic drugs like CQ.