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A Practical Synthetic Route to Cinnolines: Application to the Design and Synthesis of RSV NNI Inhibitor JNJ-8003 Analogues.
Chemistry
January 2025
Janssen Pharmaceutica NV, chemcial process R&D, BELGIUM.
The manuscript describes the development of an efficient synthetic route to cinnolines, facilitating faster access to JNJ-8003 related Respiratory Syncytial Virus (RSV) non-nucleoside (NNI) inhibitors. Starting from correctly functionalized aryl halides, a Sonogashira reaction followed by SNAr reaction with hydrazine 1,2-dicabroxylate reagents provided dihydrocinnolines directly via in situ 6-endo-dig cyclization. The dihydrocinnolines were conveniently transformed to corresponding cinnolines in one step.
View Article and Find Full Text PDFRespiratory Syncytial Virus Vaccination Is Associated With Increased Odds of Preterm Birth.
Acta Paediatr
January 2025
Institute of Clinical Medicine and Kuopio Pediatric Research Unit (KUPRU), University of Eastern Finland, Kuopio, Finland.
Aim: To analyse whether respiratory syncytial virus (RSV) vaccination during pregnancy increases the odds of preterm birth.
Methods: A rapid review and meta-analysis was performed. The main outcome was the risk of preterm (gestational week less than 37) birth.
Background: Multiple prophylactic products are now available to protect against respiratory syncytial virus (RSV) in different age groups. Assessing the pre-intervention burden of RSV infections across various severity levels and risk groups is crucial, as it provides a baseline for evaluating the impact of these products.
Methods: We obtained monthly time series data on hospitalizations, intensive care unit (ICU) admissions, and deaths by age group, ZIP code, and cause for New York state from 2005 to 2019.
Phylogenetic and Sequence Analyses of the Variable Region in the Glycoprotein Gene of the Respiratory Syncytial Virus Isolated from Iraqi Patients.
Malays J Med Sci
December 2024
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
Background: Respiratory syncytial virus (RSV) is a common aetiological agent that causes respiratory infections, especially among infants. Identifying circulating RSV genotypes is an essential strategy for understanding the spread of the virus in a certain area. Sequencing the variable regions of the attachment glycoprotein (G) gene of RSV is a quick and direct approach for identifying the genotypes.
View Article and Find Full Text PDFAn engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.
J Biol Chem
January 2025
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. Electronic address:
Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.
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