Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin
Abstract The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a wide...
Saved in:
| Published in: | Thrombosis and haemostasis Vol. 120; no. 12; pp. 1700 - 1715 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Rüdigerstraße 14, 70469 Stuttgart, Germany
Georg Thieme Verlag KG
01.12.2020
|
| Subjects: | |
| ISSN: | 0340-6245, 2567-689X, 2567-689X |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Abstract
The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-
O
or 6-
O
sulfate groups than on
N
-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the
Coronaviridae
. |
|---|---|
| AbstractList | The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-
or 6-
sulfate groups than on
-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the
. The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae. Abstract The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2- O or 6- O sulfate groups than on N -sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae . |
| Author | Li, Yong Mancini, Nicasio Meneghetti, Maria C. Z. Procter, Patricia Elli, Stefano Rudd, Timothy R. Guimond, Scott E. Nader, Helena B. Lima, Marcelo A. Bisio, Antonella Ferro, Vito Yates, Edwin A. Turnbull, Jeremy E. Pagani, Isabel Clementi, Massimo Gandhi, Neha S. Su, Dunhao Fernig, David G. Vicenzi, Elisa Miller, Gavin J. Forsyth, Nicholas R. Skidmore, Mark A. Mycroft-West, Courtney J. Nunes, Quentin M. Guerrini, Marco |
| Author_xml | – sequence: 1 givenname: Courtney J. surname: Mycroft-West fullname: Mycroft-West, Courtney J. organization: Molecular and Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, United Kingdom – sequence: 2 givenname: Dunhao surname: Su fullname: Su, Dunhao organization: Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom – sequence: 3 givenname: Isabel surname: Pagani fullname: Pagani, Isabel organization: Viral Pathogenesis and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy – sequence: 4 givenname: Timothy R. surname: Rudd fullname: Rudd, Timothy R. organization: Analytical and Biological Sciences Division, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom – sequence: 5 givenname: Stefano surname: Elli fullname: Elli, Stefano organization: Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy – sequence: 6 givenname: Neha S. surname: Gandhi fullname: Gandhi, Neha S. organization: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia – sequence: 7 givenname: Scott E. surname: Guimond fullname: Guimond, Scott E. organization: School of Medicine, Keele University, Newcastle-Under-Lyme, Staffordshire, United Kingdom – sequence: 8 givenname: Gavin J. surname: Miller fullname: Miller, Gavin J. organization: School of Chemical and Physical Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, United Kingdom – sequence: 9 givenname: Maria C. Z. surname: Meneghetti fullname: Meneghetti, Maria C. Z. organization: Biochemistry Department, Federal University of São Paulo (UNIFESP), São Paulo, SP Brazil – sequence: 10 givenname: Helena B. surname: Nader fullname: Nader, Helena B. organization: Biochemistry Department, Federal University of São Paulo (UNIFESP), São Paulo, SP Brazil – sequence: 11 givenname: Yong surname: Li fullname: Li, Yong organization: Keele University, School of Life Sciences, Huxley Building, Newcastle-Under-Lyme – sequence: 12 givenname: Quentin M. surname: Nunes fullname: Nunes, Quentin M. organization: Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom – sequence: 13 givenname: Patricia surname: Procter fullname: Procter, Patricia organization: Molecular and Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, United Kingdom – sequence: 14 givenname: Nicasio surname: Mancini fullname: Mancini, Nicasio organization: Università Vita-Salute San Raffaele, Milan, Italy – sequence: 15 givenname: Massimo surname: Clementi fullname: Clementi, Massimo organization: Università Vita-Salute San Raffaele, Milan, Italy – sequence: 16 givenname: Antonella surname: Bisio fullname: Bisio, Antonella organization: Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy – sequence: 17 givenname: Nicholas R. surname: Forsyth fullname: Forsyth, Nicholas R. organization: Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Hartshill, Stoke-on-Trent, Staffordshire, United Kingdom – sequence: 18 givenname: Vito surname: Ferro fullname: Ferro, Vito organization: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia – sequence: 19 givenname: Jeremy E. surname: Turnbull fullname: Turnbull, Jeremy E. organization: Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom – sequence: 20 givenname: Marco surname: Guerrini fullname: Guerrini, Marco organization: Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy – sequence: 21 givenname: David G. surname: Fernig fullname: Fernig, David G. organization: Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom – sequence: 22 givenname: Elisa surname: Vicenzi fullname: Vicenzi, Elisa organization: Viral Pathogenesis and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy – sequence: 23 givenname: Edwin A. surname: Yates fullname: Yates, Edwin A. organization: Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom – sequence: 24 givenname: Marcelo A. surname: Lima fullname: Lima, Marcelo A. organization: Molecular and Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, United Kingdom – sequence: 25 givenname: Mark A. orcidid: 0000-0002-0287-5594 surname: Skidmore fullname: Skidmore, Mark A. email: m.a.skidmore@keele.ac.uk organization: Keele University, School of Life Sciences, Huxley Building, Newcastle-Under-Lyme |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33368089$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1kctO3DAUhq0KVAbotsvKSzamviRx3B0Mt5FGqsQU1J3lJGc6pokdbAfEU_DK9Yh0cywd_-f2_cfowHkHCH1l9JzRsvweCaUFJUxyJpj6hBa8rCSpavX7AC2oyF8VL8ojdBzjE6WsKlT5GR0JIaqa1mqB3u9gNME6vHI729gU8RL6fupNyJkXE613uHnDm4v7DVn6R8J_4E0KU5umYHp8BSO4DlwL2G9x2kEuShBMm_Z1c2oz2r85MnwPLYzJB3JpXWfdH3zlB5NHv9q0w_Mep-hwa_oIX-b3BD3cXP9a3pH1z9vV8mJN2oLXiYARbUupkpxKoUopqJSMKZFZVBUVDcvHiVKoLjMqMpiikzVvuMqiclszKk7Q2UffMfjnCWLSg41tPt048FPUvJAZHivEXvptlk7NAJ0egx1MeNP_IWYB-RCknYUB9JOfgsvLa0b13iQd9d4kPZsk_gEUZYCV |
| CitedBy_id | crossref_primary_10_1016_j_apsb_2022_01_019 crossref_primary_10_1080_19390211_2022_2075072 crossref_primary_10_1017_cjn_2023_39 crossref_primary_10_1055_a_1815_2142 crossref_primary_10_3389_fchem_2022_871509 crossref_primary_10_1002_jhet_4349 crossref_primary_10_1007_s12551_022_00999_7 crossref_primary_10_3390_v15010237 crossref_primary_10_1080_07391102_2023_2167114 crossref_primary_10_1016_j_procbio_2022_02_012 crossref_primary_10_3389_fphar_2025_1585762 crossref_primary_10_3390_antiox10060881 crossref_primary_10_1007_s10719_021_10018_8 crossref_primary_10_1134_S1068162022060152 crossref_primary_10_3389_fcimb_2025_1552116 crossref_primary_10_1002_1873_3468_14173 crossref_primary_10_1055_s_0041_1741072 crossref_primary_10_3390_biom15070931 crossref_primary_10_1016_j_sbi_2022_102402 crossref_primary_10_1111_febs_16096 crossref_primary_10_1055_a_1807_0168 crossref_primary_10_1002_pgr2_70028 crossref_primary_10_1038_s41598_024_84276_5 crossref_primary_10_3390_jcm11154464 crossref_primary_10_1016_j_cej_2025_164066 crossref_primary_10_1016_j_jinorgbio_2022_111899 crossref_primary_10_1002_rth2_12638 crossref_primary_10_3390_reactions3030031 crossref_primary_10_1007_s12032_021_01533_7 crossref_primary_10_1093_glycob_cwac042 crossref_primary_10_1128_CMR_00109_21 crossref_primary_10_1038_s41598_022_10293_x crossref_primary_10_3389_fphar_2023_1159363 crossref_primary_10_1016_j_burns_2025_107518 crossref_primary_10_3390_v14010035 crossref_primary_10_3389_fmed_2024_1364657 crossref_primary_10_1002_chem_202202599 crossref_primary_10_3390_ijms23094805 crossref_primary_10_1016_j_clim_2023_109836 crossref_primary_10_1016_j_trac_2023_117243 crossref_primary_10_1038_s41392_024_01741_3 crossref_primary_10_3390_pharmaceutics13111768 crossref_primary_10_1016_j_ab_2023_115223 crossref_primary_10_1177_0310057X251322783 crossref_primary_10_1021_acschembio_5c00206 crossref_primary_10_1073_pnas_2404892121 crossref_primary_10_3390_ijms242216115 crossref_primary_10_1055_s_0042_1749395 crossref_primary_10_1038_s41392_022_00884_5 crossref_primary_10_1080_21548331_2021_2007648 crossref_primary_10_1038_s41590_021_01114_w crossref_primary_10_1055_s_0042_1760264 crossref_primary_10_1002_tcr_202100173 crossref_primary_10_3389_fmolb_2021_637550 crossref_primary_10_7554_eLife_95708_3 crossref_primary_10_1016_j_jbc_2021_101507 crossref_primary_10_3390_ijms222011013 crossref_primary_10_3389_fpls_2023_1275228 crossref_primary_10_3389_fcvm_2023_1282637 crossref_primary_10_3390_jcm10051073 crossref_primary_10_1016_j_ijbiomac_2022_12_090 crossref_primary_10_1186_s40560_024_00723_5 crossref_primary_10_3389_fmed_2021_615333 crossref_primary_10_1016_j_ejmech_2023_115923 crossref_primary_10_1016_j_pharmthera_2023_108540 crossref_primary_10_1097_MD_0000000000028288 crossref_primary_10_1002_cpt_2504 crossref_primary_10_3390_brainsci13030415 crossref_primary_10_1038_s41598_024_70064_8 crossref_primary_10_1111_bcp_14714 crossref_primary_10_3389_fmicb_2025_1546946 crossref_primary_10_1093_glycob_cwae084 crossref_primary_10_3390_ijms221910730 crossref_primary_10_3390_ph17101362 crossref_primary_10_1186_s40659_023_00434_5 crossref_primary_10_1177_1358863X231159945 crossref_primary_10_3390_biomedicines9111544 crossref_primary_10_3390_app11083512 crossref_primary_10_3390_life12060915 crossref_primary_10_1016_j_carbpol_2022_119818 crossref_primary_10_3390_ph16101385 crossref_primary_10_1002_pgr2_70032 crossref_primary_10_1016_j_synbio_2022_10_002 crossref_primary_10_3389_fmicb_2022_789882 crossref_primary_10_1038_s41467_025_57362_z crossref_primary_10_7554_eLife_95708 crossref_primary_10_1016_j_addr_2022_114195 crossref_primary_10_3390_microorganisms9061238 crossref_primary_10_1056_NEJMoa2105911 crossref_primary_10_1371_journal_ppat_1012203 crossref_primary_10_3390_biom15060778 crossref_primary_10_3390_molecules29235809 crossref_primary_10_3389_fimmu_2025_1460089 crossref_primary_10_1055_s_0041_1726034 crossref_primary_10_3389_fcell_2021_695970 crossref_primary_10_3390_biom11121812 crossref_primary_10_1134_S0026893325700128 crossref_primary_10_1039_D1SC04832E crossref_primary_10_3390_ijms22126574 crossref_primary_10_1159_000519542 crossref_primary_10_1073_pnas_2203167119 crossref_primary_10_1016_j_jbc_2021_101207 crossref_primary_10_1042_EBC20230093 crossref_primary_10_3390_molecules28176413 crossref_primary_10_1021_acscentsci_1c01293 crossref_primary_10_1016_j_jmb_2025_169437 crossref_primary_10_3390_molecules27165322 crossref_primary_10_1016_j_ijbiomac_2021_04_148 crossref_primary_10_3390_ijms23031716 crossref_primary_10_1055_a_1667_7534 crossref_primary_10_1007_s11010_021_04204_3 crossref_primary_10_3390_ijms24032634 crossref_primary_10_1039_D3PY01217D crossref_primary_10_1016_j_biopha_2023_114217 crossref_primary_10_1080_16583655_2021_1999068 crossref_primary_10_1007_s00894_023_05645_x crossref_primary_10_1016_j_antiviral_2023_105700 crossref_primary_10_3389_fimmu_2022_826091 crossref_primary_10_1016_j_csbj_2021_05_002 crossref_primary_10_1016_j_scitotenv_2023_168619 crossref_primary_10_2147_IJN_S496050 crossref_primary_10_1042_BCJ20220016 crossref_primary_10_3390_biomedicines10010049 crossref_primary_10_1016_j_aqrep_2025_102735 crossref_primary_10_3389_fimmu_2022_984252 crossref_primary_10_1016_j_jff_2023_105532 crossref_primary_10_1016_j_sbi_2022_102439 crossref_primary_10_3389_fmed_2021_775063 crossref_primary_10_1111_bcp_15212 crossref_primary_10_3390_cells10061412 crossref_primary_10_3390_microbiolres15020035 crossref_primary_10_1007_s00408_023_00599_6 crossref_primary_10_1016_j_carbpol_2022_120167 crossref_primary_10_3390_cells11050855 crossref_primary_10_1021_acsinfecdis_5c00250 crossref_primary_10_3389_fphar_2022_987816 crossref_primary_10_3390_v14040737 crossref_primary_10_1042_BSR20210290 crossref_primary_10_3389_fmicb_2023_1169547 crossref_primary_10_3390_ph16020271 crossref_primary_10_1128_jvi_01122_22 crossref_primary_10_3389_fnut_2025_1561119 crossref_primary_10_3389_fmicb_2022_721103 crossref_primary_10_3390_biom14080911 crossref_primary_10_3390_biom11111550 crossref_primary_10_3390_ijms23126400 crossref_primary_10_3390_ijms24065844 crossref_primary_10_1007_s10557_022_07406_z crossref_primary_10_1038_s41467_024_45419_4 crossref_primary_10_12688_f1000research_110593_2 crossref_primary_10_3390_cells10061419 crossref_primary_10_12688_f1000research_110593_3 crossref_primary_10_3389_fcvm_2022_957006 crossref_primary_10_3390_v17060741 crossref_primary_10_12688_f1000research_110593_1 crossref_primary_10_1016_j_ejps_2023_106489 crossref_primary_10_3390_ijms232113502 crossref_primary_10_1002_tcr_202100125 crossref_primary_10_1093_cvr_cvab298 crossref_primary_10_1182_blood_2021014527 crossref_primary_10_1155_2022_2044282 crossref_primary_10_3389_ijph_2021_1603975 crossref_primary_10_1016_j_ejmcr_2021_100003 crossref_primary_10_1186_s12917_022_03527_7 crossref_primary_10_1007_s10557_021_07288_7 crossref_primary_10_1093_nar_gkac345 crossref_primary_10_1021_acscentsci_1c01080 crossref_primary_10_1016_j_isci_2023_108095 crossref_primary_10_1124_pharmrev_122_000684 crossref_primary_10_3390_biom15091343 crossref_primary_10_1007_s11239_022_02681_x crossref_primary_10_1128_jvi_00057_22 |
| ContentType | Journal Article |
| Copyright | Thieme. All rights reserved. |
| Copyright_xml | – notice: Thieme. All rights reserved. |
| DBID | 0U6 CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1055/s-0040-1721319 |
| DatabaseName | Thieme Connect Journals Open Access Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: 0U6 name: Thieme Connect Journals Open Access url: http://open.thieme.com sourceTypes: Publisher – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 2567-689X |
| EndPage | 1715 |
| ExternalDocumentID | 33368089 10_1055_s_0040_1721319 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: Biotechnology and Biological Sciences Research Council grantid: BB/L023717/1 – fundername: BB/L023717/1 grantid: Biotechnology and Biological Sciences Research Council |
| GroupedDBID | --- .55 .GJ 0R~ 0U6 0VX 123 1KJ 4.4 53G 5RE AAQQT ABJNI ABOCM ACGFO ACGFS AENEX AFFNX AHRSK ALMA_UNASSIGNED_HOLDINGS BR6 C45 CS3 DU5 EBS EJD F5P H13 J5H OVD P2P RTC RTE SJN TEORI X7M ZGI ZXP CGR CUY CVF ECM EIF NPM 7X8 |
| ID | FETCH-LOGICAL-c428t-ea3cc00972073957307711930406603b10893539d05543194d782b297115f8103 |
| IEDL.DBID | 0U6 |
| ISICitedReferencesCount | 237 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000601223000008&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0340-6245 2567-689X |
| IngestDate | Fri Jul 11 13:11:56 EDT 2025 Thu Jan 02 22:56:42 EST 2025 Sun Nov 24 15:00:54 EST 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 12 |
| Keywords | heparin COVID-19 SARS-CoV-2 RBD surface plasmon resonance molecular modelling coronavirus circular dichroism S1 spike |
| Language | English |
| License | Thieme. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c428t-ea3cc00972073957307711930406603b10893539d05543194d782b297115f8103 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0002-0287-5594 |
| OpenAccessLink | http://dx.doi.org/10.1055/s-0040-1721319 |
| PMID | 33368089 |
| PQID | 2473401430 |
| PQPubID | 23479 |
| PageCount | 16 |
| ParticipantIDs | proquest_miscellaneous_2473401430 pubmed_primary_33368089 thieme_journals_10_1055_s_0040_1721319 |
| PublicationCentury | 2000 |
| PublicationDate | 20201200 2020-Dec 20201201 |
| PublicationDateYYYYMMDD | 2020-12-01 |
| PublicationDate_xml | – month: 12 year: 2020 text: 20201200 |
| PublicationDecade | 2020 |
| PublicationPlace | Rüdigerstraße 14, 70469 Stuttgart, Germany |
| PublicationPlace_xml | – name: Rüdigerstraße 14, 70469 Stuttgart, Germany – name: Germany |
| PublicationTitle | Thrombosis and haemostasis |
| PublicationTitleAlternate | Thromb Haemost |
| PublicationYear | 2020 |
| Publisher | Georg Thieme Verlag KG |
| Publisher_xml | – name: Georg Thieme Verlag KG |
| SSID | ssj0016495 |
| Score | 2.7092712 |
| Snippet | Abstract
The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and... The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular... |
| SourceID | proquest pubmed thieme |
| SourceType | Aggregation Database Index Database Publisher |
| StartPage | 1700 |
| SubjectTerms | Animals Anticoagulants - pharmacology Anticoagulants - therapeutic use Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Blood Cells, Inflammation and Infection Chlorocebus aethiops COVID-19 - drug therapy Enoxaparin - pharmacology Enoxaparin - therapeutic use Heparin - pharmacology Heparin - therapeutic use Humans Molecular Dynamics Simulation Nebulizers and Vaporizers Protein Binding Protein Conformation Protein Domains - genetics SARS-CoV-2 - physiology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - metabolism Structure-Activity Relationship Vero Cells Virus Internalization |
| Title | Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin |
| URI | http://dx.doi.org/10.1055/s-0040-1721319 https://www.ncbi.nlm.nih.gov/pubmed/33368089 https://www.proquest.com/docview/2473401430 |
| Volume | 120 |
| WOSCitedRecordID | wos000601223000008&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1JS8QwFA6iIl7cl3EjgngLdpJ0iTcdFQUdxFGZW0jSlClqO9hR8Ff4l31JOyrqwUsoIaVp3kv7vSXfQ2gvcLkzWlMiotQ4Um1BlGaC0JRH1jKTcOMp8y_jbjfp98X1l7_jZwQ_DA8q4rPenKnCHL_nFAUtdVswuIs-4wUR9_VVAuaS2SkPx_SMv-7_C0jCxWiQ2yf77c9yNv__OS2guQY94qNa3ItowhZLaOaqiY8vo_dz66oKFviiGOQ6H1W4Yx8fXaYp9Lwq5xnD-g33jm56pFPeE3qIe55A1pFv4JOmIK6xuMwwIEPs_YX10YdxV2-YP0DbxgA47RAsdnKc-5Mx-KR8UvBo59nFzTxW0N3Z6W3nnDQlF4gBO2RErGLGeEqfOoIHX4C4DRgP3jaKAqbbAeCbkIkUVgGgh-ApIAxNBQwKs6QdsFU0WZSFXUc4S3WmLUtsamKuo0wJxblijLPYsoyqFtodS0KCSrs4hSps-VJJymOQIwC5oIXWahHJYc29IRljrliIaKH9Wmay2XOV9OH0MJSVdMKRjXA2_jtwE81SZ0v7VJUtNAmrb7fRtHkd5dXzjlc3aON-Am33-uoDFe7Knw |
| linkProvider | Thieme |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3LjtMwFLXQgIAN70d5Ggmxs5rGTlKzGzqMOqJTITqDZmfZzo0a0SYVCSPxFfwy9zouQoIFCzZRZDmK4-Mkx77H5zL2OiHtjHOp0HnpyVRbC-ukFmmpcgDpp8oHy_xFsVxOLy70x7g9uouyyn5dwxaEJ6WH70lqsRvcT7sxxB7uxut-u4l5arNxJ4IyjqYzkjxAr2aUQQJHd3Ke_4op5CrkYEkkCd5Tle0tHP-4_m9kE0-GZv329zm-_X_bfYfdiiyUHw7D5i67As09dv00xtnvsx9zoOyEDT9p1rWr-47PYLMhxSqWXFpaYePuO18dflqJWftZpG_5KhjRkokHP4qJdT3wtuLIMHlYdxy2UOyLVrv6Cx4nHIkr7HDmL97VYYcNP2q3Fm9NK8Q8tuMBOz9-fzabi5i6QXicz_QCrPQ-WAMNkUD8khQT5Ir4tHmeSDdJkCdlUpfYC0hhtCqRqbhUY6Wsmk4S-ZAdNG0DjxmvSlc5kFMofaFcXlltlbJSKlmArFI7Yq_2aBl8NSjeYRtov3UmVQVijYQwGbFHA4xmN3h4GCklJR3RI_ZmgM3sETIhLJ9lpjMEjongPPnXii_ZjfnZ6cIsTpYfnrKbKc3Pg_zlGTtAJOA5u-Yv-7r7-iIMz5_7nOin |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nb9QwEB2Vgiou5bOwfBoJcTObjZ1kza3ssmpFWSqWot4s25moEW0SNaESv4K_zNhJEBIcOHCJosRKHL9J8sbzPAPwMvLaGWtjrtLc-aTaihsrFI9zmSIKN5cupMw_ytbr-empOt6Cj-NaGC-r7M5KvEDuvNLDdV5q0fTZT9spDiPcTpu8GMrUJtOWB2Gc92bIol7TqWtwPSFr9LUcopP0V1ghlaEMSyS85j2WyZjF8Y9r_I1v0k7fs99-QKtb_73rt2F34KJsvzeeO7CF1V3Y-TBE2-_BjwP0NQordlidlbbsWrbA83OvW6UjV8bPszH7nW32P234ov7C4zdsE9LR-lQebDmU13XI6oIRz2Rh9rFfSDEe2jTlV9rOGNFXbMj_52_LsM6GLesLQ7f288Rs6Md9OFm9-7w44EMBB-7Iq-k4GuFcSBDUxwPpe5LNiDHSE6dpJOwsIraUCJXTSBCRUTInvmJjRY2SYj6LxB5sV3WFD4EVuS0sijnmLpM2LYwyUhohpMhQFLGZwIsRME0viI96mArrb62OZUZwEy2MJvCgR1I3fSYPLYTwpUfUBF71yOkRJB2C80miW-0B0gNAj_614XPYOV6u9NHh-v1juBl7Jz1oYJ7ANgGBT-GGu-rK9vJZMNCfsPHqIQ |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Heparin+Inhibits+Cellular+Invasion+by+SARS-CoV-2%3A+Structural+Dependence+of+the+Interaction+of+the+Spike+S1+Receptor-Binding+Domain+with+Heparin&rft.jtitle=Thrombosis+and+haemostasis&rft.au=Mycroft-West%2C+Courtney+J.&rft.au=Su%2C+Dunhao&rft.au=Pagani%2C+Isabel&rft.au=Rudd%2C+Timothy+R.&rft.date=2020-12-01&rft.pub=Georg+Thieme+Verlag+KG&rft.issn=0340-6245&rft.eissn=2567-689X&rft.volume=120&rft.issue=12&rft.spage=1700&rft.epage=1715&rft_id=info:doi/10.1055%2Fs-0040-1721319&rft.externalDBID=HTML_FULL_TEXT&rft.externalDocID=10_1055_s_0040_1721319 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0340-6245&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0340-6245&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0340-6245&client=summon |