Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.
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Issue Date
2024-12-16
Authors
Yang, Jiyuan
Datta, Payel
Xia, Ke
Pomin, Vitor H
Wang, Chunyu
Qiao, Mingqiang
Linhardt, Robert J
Dordick, Jonathan S
Zhang, Fuming
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Abstract
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 (K = 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.
Citation
Yang J, Datta P, Xia K, Pomin VH, Wang C, Qiao M, Linhardt RJ, Dordick JS, Zhang F. Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin. Glycoconj J. 2024 Dec;41(6):371-380. doi: 10.1007/s10719-024-10172-9. Epub 2024 Dec 16. PMID: 39680336.
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NIH [S10OD028523 and R21AI156573 (R.J.L, F.Z.), 1P20GM130460-01A1-7936 and 1R03NS110996-01A1, R01 AG069039-01/GF/NIH HHS/United States