Potential anti-SARS-CoV-2 activity of pentosan polysulfate and mucopolysaccharide polysulfate

Authors
Zhang, Fuming
He, Peng
Rodrigues, Andre L.
Jeske, Walter
Tandon, Ritesh
Bates, John T.
Bierdeman, Michael A.
Fareed, Jawed
Dordick, Jonathan
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2022-02-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution 3.0 United States
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Full Citation
Potential anti-SARS-CoV-2 activity of pentosan polysulfate and mucopolysaccharide polysulfate, F. Zhang, P. He, A. L. Rodrigues, W. Jeske, R. Tandon, J. T. Bates, M. A. Bierdeman, J. Fareed, J. Dordick, R. J. Linhardt, Pharmaceuticals, 15, 258, 2022.
Abstract
With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. SARS-CoV-2 invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen-host cell interaction. Our previous studies demonstrated that many sulfated glycans, such as heparin, fucoidans, and rhamnan sulfate have anti-SARS-CoV-2 activities. In the current study, a small library of sulfated glycans and highly negatively charged compounds, including pentosan polysulfate (PPS), mucopolysaccharide polysulfate (MPS), sulfated lactobionic acid, sulodexide, and defibrotide, was assembled and evaluated for binding to the S-proteins and inhibition of viral infectivity in vitro. These compounds inhibited the interaction of the S-protein receptor-binding domain (RBD) (wild type and different variants) with immobilized heparin, a highly sulfated HS, as determined using surface plasmon resonance (SPR). PPS and MPS showed the strongest inhibition of interaction of heparin and S-protein RBD. The competitive binding studies showed that the IC50 of PPS and MPS against the S-protein RBD binding to immobilized heparin was ~35 nM and ~9 nM, respectively, much lower than the IC50 for soluble heparin (IC50 = 56 nM). Both PPS and MPS showed stronger inhibition than heparin on the S-protein RBD or spike pseudotyped lentiviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, PPS and MPS exhibited strong antiviral activities against pseudotyped viral particles of SARS-CoV-2 containing wild-type or Delta S-proteins.
Description
Pharmaceuticals, 15, 258
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Pharmaceuticals
https://harc.rpi.edu/
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A full text version is available in DSpace@RPI
CC BY — Creative Commons Attribution