Potential anti-SARS-CoV-2 activity of pentosan polysulfate and mucopolysaccharide polysulfate
AuthorZhang, Fuming; He, Peng; Rodrigues, Andre L.; Jeske, Walter; Tandon, Ritesh; Bates, John T.; Bierdeman, Michael A.; Fareed, Jawed; Dordick, Jonathan; Linhardt, Robert J.
SubjectBiology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
Full CitationPotential 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.
MetadataShow full item record
AbstractWith 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.;
DescriptionPharmaceuticals, 15, 258; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
DepartmentThe Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
RelationshipsThe Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Pharmaceuticals; https://harc.rpi.edu/;
AccessCC BY — Creative Commons Attribution; A full text version is available in DSpace@RPI; Open Access;
The following license files are associated with this item: