The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design.
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http://dx.doi.org/10.1093/glycob/cwx092 | DOI Listing |
Virus Evol
November 2024
Center for Viral Surveillance and Serological Assessment (CeVIVAS), Instituto Butantan, Avenida Vital Brasil, 1500, Butantã, São Paulo, São Paulo 05503-900, Brazil.
Influenza A and B viruses represent significant global health threats, contributing substantially to morbidity and mortality rates. However, a comprehensive understanding of the molecular epidemiology of these viruses in Brazil, a continental-size country and a crucial hub for the entry, circulation, and dissemination of influenza viruses within South America, still needs to be improved. This study addresses this gap by consolidating data and samples across all Brazilian macroregions, as part of the Center for Viral Surveillance and Serological Assessment project, together with an extensive number of other Brazilian sequences provided by a public database during the epidemic seasons spanning 2021-23.
View Article and Find Full Text PDFInt J Pharm
January 2025
College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address:
Advanced cancer patients face a high risk of sepsis due to immune suppression and infection susceptibility. To tackle this challenge, we developed an innovative animal model that simulates the clinical scenario of late-stage cancer complicated by sepsis and designed a sialic acid (SA)-modified paclitaxel (PTX) liposome (PTX-SAL). This formulation specifically targets overactivated peripheral blood neutrophils (PBNs) by binding to L-selectin on their surface.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad-spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Key Laboratory of Medical Molecular Virology (Ministry of Education / National Health Commission / Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200033, China.
Sialic acids derived from colonic mucin glycans are crucial nutrients for enteric bacterial pathogens like . The uptake and utilization of sialic acid in depend on coordinated regulons, each activated by specific metabolites at the transcriptional level. However, the mechanisms enabling crosstalk among these regulatory circuits to synchronize gene expression remain poorly understood.
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