SPR Sensor-Based Analysis of the Inhibition of Marine Sulfated Glycans on Interactions between Monkeypox Virus Proteins and Glycosaminoglycans
Authors:
Peng He1,2, Deling Shi1,2, Yunran Li1,3, Ke Xia1,2, Seon Beom Kim4,5, Rohini Dwivedi4, Marwa Farrag4, Vitor H. Pomin4, Robert J. Linhardt1,2,3,6, Jonathan S. Dordick1,6,* and Fuming Zhang1,6,*
Affiliation:
1Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
2Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
3Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
4Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, The University of Mississippi, Oxford, MS 38677, USA
5Department of Food Science & Technology, College of Natural Resources and Life Science, Pusan National University, Miryang 46241, Republic of Korea
6Departments of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
Description:
Sulfated glycans from marine organisms are excellent sources of naturally occurring glycosaminoglycan (GAG) mimetics that demonstrate therapeutic activities, such as antiviral/microbial infection, anticoagulant, anticancer, and anti-inflammation activities. Many viruses use the heparan sulfate (HS) GAG on the surface of host cells as co-receptors for attachment and initiating cell entry. Therefore, virion–HS interactions have been targeted to develop broad-spectrum antiviral therapeutics. Here we report the potential anti-monkeypox virus (MPXV) activities of eight defined marine sulfated glycans, three fucosylated chondroitin sulfates, and three sulfated fucans extracted from the sea cucumber species Isostichopus badionotus, Holothuria floridana, and Pentacta pygmaea, and the sea urchin Lytechinus variegatus, as well as two chemically desulfated derivatives. The inhibitions of these marine sulfated glycans on MPXV A29 and A35 protein–heparin interactions were evaluated using surface plasmon resonance (SPR). These results demonstrated that the viral surface proteins of MPXV A29 and A35 bound to heparin, which is a highly sulfated HS, and sulfated glycans from sea cucumbers showed strong inhibition of MPXV A29 and A35 interactions. The study of molecular interactions between viral proteins and host cell GAGs is important in developing therapeutics for the prevention and treatment of MPXV.