| Autor: |
Clausen TM, Sandoval DR, Spliid CB, Pihl J, Painter CD, Thacker BE, Glass CA, Narayanan A, Majowicz SA, Zhang Y, Torres JL, Golden GJ, Porell R, Garretson AF, Laubach L, Feldman J, Yin X, Pu Y, Hauser B, Caradonna TM, Kellman BP, Martino C, Gordts PLSM, Leibel SL, Chanda SK, Schmidt AG, Godula K, Jose J, Corbett KD, Ward AB, Carlin AF, Esko JD |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2020 Jul 14. Date of Electronic Publication: 2020 Jul 14. |
| DOI: |
10.1101/2020.07.14.201616 |
| Abstrakt: |
We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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