The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
116 views
Information Technology Daily
2021 FEB 09 (NewsRx) By a News Reporter-Staff News Editor at Information Technology Daily Investigators publish new report on Information Technology - Data Recovery. According to news reporting originating in Guangzhou, People’s Republic of China, by NewsRx journalists, research stated, “In this paper, we focus on the false data injection attacks (FDIAs) on state estimation and corresponding countermeasures for data recovery in smart grid. Without the information about the topology and parameters of systems, two data-driven attacks (DDAs) with noisy measurements are constructed, which can escape the detection from the residue-based bad data detection (BDD) in state estimator.”
In a new study published in
Journal of Extracellular Vesicles, Chen-Yu Zhang s group and Antonio Vidal-Puig s group at University of Cambridge report that pancreatic β cells secrete miR-29 family members (miR-29a, miR-29b and miR-29c) in response to high levels of free fatty acids (FFAs). These β cell-derived miR-29s are delivered to the liver, promoting insulin resistance and enhancing hepatic glucose output.
Over 100 years after insulin was discovered, it was believed that pancreatic β cells only secreted a single hormone insulin. Pancreatic β cell-derived insulin regulates glucose homeostasis by binding with the insulin receptors located in the liver, skeletal muscle, adipose tissues and other peripheral organs. The discovery of insulin and its receptor was essential to understand the mechanisms controlling glucose homeostasis and the pathogenesis of type 2 diabetes defined by defective insulin secretion, signal transduction and insulin resistance. However, glucose homeos
In a new study published in
Journal of Extracellular Vesicles, Chen-Yu Zhang s group at Nanjing University, School of Life Sciences, and Antonio Vidal-Puig s group at University of Cambridge report that pancreatic β cells secrete miR-29 family members (miR-29s) via exosomes in response to high levels of free fatty acids (FFAs). Theses β cell-derived exosomal miR-29s regulate glucose homeostasis through their manipulations on glucose output in liver.
Previously, Chen-Yu Zhang s group identified extracellular miRNA as a new form of cell-to-cell communication. They are among the first that reported the selective secretion of miRNAs under different physiological or pathological states; also, the uptake and function of secreted miRNAs in recipient cells. In the past decade, intensive studies have revealed the role of extracellular miRNAs in a range of biological processes. Thus, as a newly-emerged secretory factor, more insightful studies are needed to further reveal its relevance t