Sulfated Glycans Inhibit the Interaction of MERS-CoV Receptor Binding Domain with Heparin

Author:

Yang Jiyuan12,Song Yuefan2ORCID,Jin Weihua3ORCID,Xia Ke2ORCID,Burnett Grace C.4,Qiao Wanjin1,Bates John T.4ORCID,Pomin Vitor H.5ORCID,Wang Chunyu2,Qiao Mingqiang1,Linhardt Robert J.26ORCID,Dordick Jonathan S.6,Zhang Fuming6ORCID

Affiliation:

1. The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China

2. Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

3. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China

4. Department of Cell & Molecular Biology, The University of Mississippi Medical Center, Jackson, MS 39216, USA

5. Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, The University of Mississippi, Oxford, MS 38677, USA

6. Departments of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.

Funder

NIH

National Science Foundation GlycoMIP

New York State Biodefense Commercialization Fund

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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