近日，美国加州大学圣迭戈分校Jeffrey D. Esko、Thomas Mandel Clausen等研究人员合作发现，SARS-CoV-2感染依赖细胞硫酸乙酰肝素和ACE2。这一研究成果于2020年9月14日在线发表在《细胞》上。

Title: SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2

Author: Thomas Mandel Clausen, Daniel R. Sandoval, Charlotte B. Spliid, Jessica Pihl, Hailee R. Perrett, Chelsea D. Painter, Anoop Narayanan, Sydney A. Majowicz, Elizabeth M. Kwong, Rachael N. McVicar, Bryan E. Thacker, Charles A. Glass, Zhang Yang, Jonathan L. Torres, Gregory J. Golden, Phillip L. Bartels, Ryan Porell, Aaron F. Garretson, Logan Laubach, Jared Feldman, Xin Yin, Yuan Pu, Blake Hauser, Timothy M. Caradonna, Benjamin P. Kellman, Cameron Martino, Philip L.S.M. Gordts, Sumit K. Chanda, Aaron G. Schmidt, Kamil Godula, Sandra L. Leibel, Joyce Jose, Kevin D. Corbett, Andrew B. Ward, Aaron F. Carlin, Jeffrey D. Esko

Issue&Volume: 2020-09-14

Abstract: We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2 binding site. Both ACE2 and heparin can bind independently to spike protein in vitro and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities.

DOI: 10.1016/j.cell.2020.09.033

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31230-7