Cargando…
Heparan 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
The 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 surfac...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231436/ https://www.ncbi.nlm.nih.gov/pubmed/34179075 http://dx.doi.org/10.3389/fmolb.2021.649575 |
_version_ | 1783713424329408512 |
---|---|
author | Yue, Jingwen Jin, Weihua Yang, Hua Faulkner, John Song, Xuehong Qiu, Hong Teng, Michael Azadi, Parastoo Zhang, Fuming Linhardt, Robert J. Wang, Lianchun |
author_facet | Yue, Jingwen Jin, Weihua Yang, Hua Faulkner, John Song, Xuehong Qiu, Hong Teng, Michael Azadi, Parastoo Zhang, Fuming Linhardt, Robert J. Wang, Lianchun |
author_sort | Yue, Jingwen |
collection | PubMed |
description | The 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. |
format | Online Article Text |
id | pubmed-8231436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82314362021-06-26 Heparan 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 Yue, Jingwen Jin, Weihua Yang, Hua Faulkner, John Song, Xuehong Qiu, Hong Teng, Michael Azadi, Parastoo Zhang, Fuming Linhardt, Robert J. Wang, Lianchun Front Mol Biosci Molecular Biosciences The 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. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8231436/ /pubmed/34179075 http://dx.doi.org/10.3389/fmolb.2021.649575 Text en Copyright © 2021 Yue, Jin, Yang, Faulkner, Song, Qiu, Teng, Azadi, Zhang, Linhardt and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Yue, Jingwen Jin, Weihua Yang, Hua Faulkner, John Song, Xuehong Qiu, Hong Teng, Michael Azadi, Parastoo Zhang, Fuming Linhardt, Robert J. Wang, Lianchun Heparan 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 |
title | Heparan 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 |
title_full | Heparan 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 |
title_fullStr | Heparan 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 |
title_full_unstemmed | Heparan 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 |
title_short | Heparan 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 |
title_sort | heparan 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 |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231436/ https://www.ncbi.nlm.nih.gov/pubmed/34179075 http://dx.doi.org/10.3389/fmolb.2021.649575 |
work_keys_str_mv | AT yuejingwen heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT jinweihua heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT yanghua heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT faulknerjohn heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT songxuehong heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT qiuhong heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT tengmichael heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT azadiparastoo heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT zhangfuming heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT linhardtrobertj heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer AT wanglianchun heparansulfatefacilitatesspikeproteinmediatedsarscov2hostcellinvasionandcontributestoincreasedinfectionofsarscov2g614mutantandinlungcancer |