Interactions of heparin with key glycoproteins of human respiratory syncytial virus

Deling Shi; Peng He; Yuefan Song; Robert J Linhardt; Jonathan S Dordick; Lianli Chi; Fuming Zhang

doi:10.3389/fmolb.2023.1151174

Interactions of heparin with key glycoproteins of human respiratory syncytial virus

Front Mol Biosci. 2023 Apr 14:10:1151174. doi: 10.3389/fmolb.2023.1151174. eCollection 2023.

Authors

Deling Shi^{1

2}, Peng He², Yuefan Song², Robert J Linhardt², Jonathan S Dordick², Lianli Chi¹, Fuming Zhang²

Affiliations

¹ National Glycoengineering Research Center, Shandong University, Qingdao, China.
² Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.

Abstract

Introduction: The unexpected surge of respiratory syncytial virus (RSV) cases following pandemic phase of COVID-19 has drawn much public attention. Drawing on the latest antiviral research, revisiting this heightened annual outbreak of respiratory disease could lead to new treatments. The ability of sulfated polysaccharides to compete for a variety of viruses binding to cell surface heparan sulfate, suggests several drugs that might have therapeutic potential for targeting RSV-glycosaminoglycan interactions. Methods: In the current study, the binding affinity and kinetics of two RSV glycoproteins (RSV-G protein and RSV-F protein) to heparin were investigated by surface plasmon resonance. Furthermore, solution competition studies using heparin oligosaccharides of different lengths indicated that the binding of RSV-G protein to heparin is size-dependent, whereas RSV-F protein did not show any chain length preference. Results and discussion: The two RSV glycoproteins have slightly different preferences for heparin sulfation patterns, but the N-sulfo group in heparin was most critical for the binding of heparin to both RSV-G protein and RSV-F protein. Finally, pentosan polysulfate and mucopolysaccharide polysulfate were evaluated for their inhibition of the RSV-G protein and RSV-F protein-heparin interaction, and both highly negative compounds showed strong inhibition.

Keywords: glycoproteins; heparin; human respiratory syncytial virus; mucopolysaccharide polysulfate; pentosan polysulfate.

Grants and funding

This work was supported by the NIH (S10OD028523, R21AI156573) and GlycoMIP, a National Science Foundation Materials Innovation Platform funded through Cooperative Agreement DMR-1933525; New York State Biodefense Commercialization Fund.