《bioRxiv,5月17日,Binding of the SARS-CoV-2 Spike Protein to Glycans》

  • 来源专题:COVID-19科研动态监测
  • 编译者: xuwenwhlib
  • 发布时间:2020-05-18
  • Binding of the SARS-CoV-2 Spike Protein to Glycans

    Wei Hao, Bo Ma, Ziheng Li, Xiaoyu Wang, Xiaopan Gao, Yaohao Li, Bo Qin, Shiying Shang, Sheng Cui, Zhongping Tan

    doi: https://doi.org/10.1101/2020.05.17.100537

    Abstract

    The 2019 novel coronavirus (SARS-CoV-2) is the seventh human coronavirus. The pandemic of this virus has caused a high number of deaths in the world. In order to more efficiently combat this pandemic, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the initial attachment of the virus to cell-surface glycans like heparan sulfate (HS) proteoglycans and sialic acid-containing oligosaccharides. In this study, we used glycan microarray technology to study the binding of the SARS-CoV-2 spike protein (S protein) to HS and sialic acid. Our results indicated that the S protein can bind to HS in a sulfation-dependent manner and the length of HS appears not to be a critical factor for the binding. No binding with sialic acid residues was detected. In addition, we applied sequence alignment and molecular docking to analyze and explain the observed binding results. Our results suggested that HS may stabilize the open conformation of the S protein to promote the subsequent binding of the S protein to the virus entry receptor ACE2. Overall, this work supports the potential importance of HS in SARS-CoV-2 infection and in the development of antiviral agents.

  • 原文来源:https://www.biorxiv.org/content/10.1101/2020.05.17.100537v1
相关报告
  • 《BioRxiv,2月27日,Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-02-28
    • Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2 Tamina Park, Sang-Yeop Lee, Seil Kim, Mi Jeong Kim, Hong Gi Kim, Sangmi Jun, Seung Il Kim, Bum Tae Kim, Edmond Changkyun Park, Daeui Park doi: https://doi.org/10.1101/2020.02.22.951178 Abstract Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.
  • 《Nature,9月17日,Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-10-13
    • Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion Donald J. Benton, Antoni G. Wrobel, Pengqi Xu, Chloë Roustan, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel & Steven J. Gamblin Nature (2020) Abstract SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1–4, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus Spike glycoprotein, S5–7. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2 components that remain associated following cleavage8–10. Fusion activation following receptor binding is proposed to involve the exposure of a second proteolytic site (S2’), cleavage of which is required for the fusion peptide release11,12. We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. The ten structures describe ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of an S1 subdomain following ACE2 binding, that disrupts interactions with S2, notably involving Asp61413–15, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.