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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorYue, Jingwen
dc.contributor.authorJin, Weihua
dc.contributor.authorYang, Hua
dc.contributor.authorFaulkner, John
dc.contributor.authorSong, Xuehong
dc.contributor.authorQiu, Hong
dc.contributor.authorTeng, Michael
dc.contributor.authorAzadi, Parastoo
dc.contributor.authorZhang, Fuming
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorWang, Lianchun
dc.date2021
dc.date.accessioned2022-06-21T13:51:28Z
dc.date.available2022-06-21T13:51:28Z
dc.date.issued2021-06-11
dc.identifier.citationHeparan sulfate facilitates spike protein-mediated SARS-Cov-2 host cell invasion and contributes to increased infection of SARS-Cov-2 G614 mutant and in lung cancer, J. Yue, W. Jin, H. Yang, J. Faulkner, X. Song1, H. Qiu, M. Teng, H. Choe, P. Azadi, F. Zhang, R. J. Linhardt, L. Wang, Frontiers in Molecular Biosciences, 8, 649575, 2021
dc.identifier.issn2296889X
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5037
dc.identifier.urihttps://doi.org/10.3389/fmolb.2021.649575
dc.descriptionFrontiers in Molecular Biosciences, 8, 649575
dc.descriptionNote : 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.
dc.description.abstractThe severe acute respiratory syndrome (SARS)-like coronavirus disease (COVID-19) is caused by SARS-CoV-2 and has been a serious threat to global public health with limited treatment. Cellular heparan sulfate (HS) has been found to bind SARS-CoV-2 spike protein (SV2-S) and co-operate with cell surface receptor angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 infection of host cells. In this study, we determined that host cell surface SV2-S binding depends on and correlates with host cell surface HS expression. This binding is required for SARS-Cov-2 virus to infect host cells and can be blocked by heparin lyase, HS antagonist surfen, heparin, and heparin derivatives. The binding of heparin/HS to SV2-S is mainly determined by its overall sulfation with potential, minor contribution of specific SV2-S binding motifs. The higher binding affinity of SV2-S G614 mutant to heparin and upregulated HS expression may be one of the mechanisms underlying the higher infectivity of the SARS-CoV-2 G614 variant and the high vulnerability of lung cancer patients to SARS-CoV-2 infection, respectively. The higher host cell infection by SARS-CoV-2 G614 variant pseudovirus and the increased infection caused by upregulated HS expression both can be effectively blocked by heparin lyase and heparin, and possibly surfen and heparin derivatives too. Our findings support blocking HS-SV2-S interaction may provide one addition to achieve effective prevention and/treatment of COVID-19.
dc.description.sponsorshipNational Institutes of Health
dc.languageen_US
dc.language.isoENG
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofFrontiers in Molecular Biosciences
dc.relation.urihttps://harc.rpi.edu/
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleHeparan sulfate facilitates spike protein-mediated SARS-Cov-2 host cell invasion and contributes to increased infection of SARS-Cov-2 G614 mutant and in lung canceren_US
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.accessRightsOpen Access
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.3389/fmolb.2021.649575
dc.rights.holderCC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.volume8


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Except where otherwise noted, this item's license is described as CC BY — Creative Commons Attribution