Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin
Authors:
Jiyuan Yang, Payel Datta, Ke Xia, Vitor H. Pomin, Chunyu Wang, Mingqiang Qiao, Robert J. Linhardt, Jonathan S. Dordick, Fuming Zhang
Affiliation:
Departments of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; The Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai University, Tianjin 300071, P.R. China; Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Life Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA
Description:
Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection. In the current study, the interactions between DENV envelope protein (from Type 2 DENV) and heparin (a surrogate for HS) were analyzed using competition solution SPR. Results demonstrate that heparin binds to DENV envelope protein with high affinity ( KD = 8.83 nM). Competitive Solution SPR assays using surface-immobilized heparin and a series of naturally-sourced and semi-synthetic sulfated glycans demonstrated significant inhibitory activity against the binding of DENV envelope proteins to heparin. This study of molecular interactions could provide insights into the development of therapeutics for DENV infection.
Publications:
- Jiyuan Yang; Payel Datta; Ke Xia; Vitor H. Pomin; Chunyu Wang; Mingqiang Qiao; Robert J. Linhardt; Jonathan S. Dordick; Fuming Zhang; Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin; Glycoconjugate Journal, 2024
Tags:
Glycosaminoglycans Heparan sulfate Heparin Surface plasmon resonanceRelated Chronicles:
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