The objective is to characterize the circulating RSV strains collected from infants in South Africa during 2015-2017.Ī subset of 150 RSV-positive samples obtained in South Africa from HIV-unexposed and HIV-exposed-uninfected infants from 2015 to 2017, were selected for high-throughput next-generation sequencing of the RSV F and G glycoprotein genes. Monitoring RSV glycoprotein sequences is critical for understanding RSV epidemiology and viral antigenicity in the effort to develop anti-RSV prophylactics and therapeutics. RSV is a leading cause of lower respiratory tract infection in infants. ![]() The INFORM-RSV 2017–2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and mAbs under development. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains with high frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. Most RSV were from infants 24 hours (70.5%) with no differences in subtype distribution. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. 31.0%) and in all countries except South Africa. RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% vs. During the pilot season (2017–2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, the Netherlands, Finland, Japan, Brazil, South Africa, and Australia). INFORM-RSV is a multi-year clinical study designed to describe the global molecular epidemiology of RSV in children under five years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. The double-stapled bundle chp-ds and the triple-stapled bundle chp-ts were rationally designed to have high potency they can form a tight three-helix bundle with NtHR helix, thus potently targeting NtHR–CtHR interactions involved in RSV-F TOH motif through a competitive disruption mechanism. Molecular simulations revealed that the double and triple stapling can effectively stabilize the structured conformation of α-helical bundles, whereas the free conformation of single-stapled bundles still remain intrinsically disordered in solvent. Two chp helices were stapled together in a parallel manner with single, double or triple disulfide bridges, thus systematically resulting in seven disulfide-stapled α-helical bundles. A core binding site in CtHR C-terminus was identified, which represents a 13-mer chp peptide and can effectively interact with NtHR helix in native ordered conformation but would become largely disordered when splitting from the protein context of CtHR helix. ![]() Interaction analysis between NtHR and CtHR revealed that the C-terminal tail of CtHR packs tightly against NtHR as compared to the N-terminal and middle regions of CtHR. In TOH motif, three N-terminal heptad repeat (NtHR) helices form a trimeric coiled-coil core and other three C-terminal heptad repeat (CtHR) helices add to the core in an antiparallel manner. Here, we reported the disulfide-stapled design of α-helical bundle to target the trimer-of-hairpins (TOH) motif of RSV F glycoprotein, which is the central regulatory module that triggers viral membrane fusion event. ![]() Targeting F glycoprotein has been recognized as a promising antiviral therapeutic strategy against RSV infection. The RSV F glycoprotein is a class I fusion protein that mediates viral entry into host cells and is a major target of neutralizing antibodies. Human respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infections worldwide in infants and young children.
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