The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.
Metabolic illnesses, including obesity and type 2 diabetes, have become worldwide epidemics that have an effect on public health. Clinical investigations and further exploration of these mechanisms could lead to innovative, effective, and personalized treatment strategies for individuals. It is important to screen biomarkers in previous studies to discover what is missing. Glucagon-like peptide-1′s role in insulin secretion and glucose control highlights its diagnostic and therapeutic potential. Glucose-dependent insulinotropic peptide’s influence on postprandial satiety and weight management signifies its importance in understanding metabolic processes. Monocyte chemoattractant protein-1′s involvement in inflammation and insulin resistance underlines its value as a diagnostic marker. Insulin-like growth factor-binding protein-7’s association with insulin sensitivity and kidney function presents it as a potential target for these diseases’ management. In validating these biomarkers, it will be easier to reflect pathophysiological processes, and clinicians will be able to better assess disease severity, monitor disease progression, and tailor treatment strategies. The purpose of the study was to elucidate the significance of identifying novel biomarkers for type 2 diabetes mellitus and obesity, which can revolutionize early detection, risk assessment, and personalized treatment strategies. Standard literature searches of PubMed (MEDLINE), EMBASE, and Cochrane Library were conducted in the year 2023 to identify both original RCTs and recent systematic reviews that have explored the importance of identifying novel biomarkers for T2D and obesity. This search produced 1964 results, and then was reduced to randomized controlled trial and systematic reviews, producing 145 results and 44 results, respectively. Researchers have discovered potential associations between type 2 diabetes mellitus and obesity and the biomarkers glucagon-like peptide-1, glucose-dependent insulinotropic peptide, monocyte chemoattractant protein-1, and insulin-like growth factor-binding protein-7. Understanding the role of those biomarkers in disease pathogenesis offers hope for improving diagnostics, personalized treatment, and prevention strategies.
One in three women of reproductive age is obese. The mainstay treatment for obesity is bariatric surgery, and the following weight reduction results in a decrease in pregnancy adverse effects, including gestational diabetes mellitus, pregnancy-induced hypertension, and macrosomia. However, nutritional and vitamin deficiencies due to changes in the gastrointestinal tract after bariatric surgery are associated with an increase in the risk of fetal growth retardation and small for gestational-age neonates. The purpose of this review was to analyze the available recent literature on the subject of the management of pregnancy after bariatric surgery. We searched for available articles from 2007 to 2023 and chose articles of the greatest scientific and clinical value. Micronutrient, vitamin, and protein supplementation is recommended in the prenatal period and throughout the pregnancy. It is advised that pregnant women with a history of bariatric surgery should be provided with regular specialist dietary care. There is still a lack of recommendations about the optimum gestational weight gain after different types of bariatric surgery and for patients of different metabolic statuses. Women of reproductive age undergoing bariatric procedures should be provided with appropriate counseling about adequate contraception, the recommended time-to-conception interval, and the positive and negative influence of bariatric surgery on perinatal outcomes.