Disclaimer: I am not a protein physicist, and what follows is simply a collection of facts on the role of the spike(S) protein in covid-19 infection driven by my curiosity about how to approach modelling and controlling covid-19 infection.

A few useful pieces of information:

  1. Coronaviruses derive their name from the spike(S) protein which gives them their spiky structure.

  2. The spike serves two purposes:

    a. Attachment at host cell surface.

    b. Entry at the host cell membrane, which allows infection to begin.

  3. The spike is also the main target of antibodies so it is a key focus of vaccine design.

  4. Scientists have found structural evidence that covid-19 S protein binds ACE2(an enzyme) with high affinity where the presence of ACE2 normally helps regulate blood pressure.

  5. Analysis of epithelial cells in the respiratory system reveals that nasal epithelial cells, specifically goblet and ciliated cells, display the highest ACE2 expression of all epithelial cells analysed. So nasal epithelial cells are a key point of entry.

Besides nasal epithelial cells, ACE2 is also found in cells in the cornea of the eye and intestine linings [1]. So these represent other routes of infection, and this motivates the creation of a cell atlas for covid-19.


If we focus on the local interaction of the covid-19 spike protein with ACE2, then we may try modelling the dynamic behaviour of the covid-19 spike protein. Some researchers at Max Planck are actively working on this using biophysical models running on supercomputers.

However, if we want to model the interactions of covid-19 with the human body i.e. the progression of infection …I think this is a much more complex task. For this we may need machine learning models as pursued in [4].


  1. Sungnak, W., Huang, N., Bécavin, C. et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med (2020). https://doi.org/10.1038/s41591-020-0868-6

  2. Alexandra C.Walls, Young-Jun Park, Alejandra Tortorici, Abigail Wall, Andrew T.McGuire, David Veesler. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020.

  3. Ratul Chowdhury & Costas D. Maranas. Biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor explains increased COVID-19 pathogenesis. biorxiv. 2020.

  4. Wanglong Gou, Yuanqing Fu, Liang Yue, Geng-dong Chen, Xue Cai, Menglei Shuai, Fengzhe Xu, Xiao Yi, Hao Chen, Yi Judy Zhu, Mian-li Xiao, Zengliang Jiang, Zelei Miao, Congmei Xiao, Bo Shen, Xiaomai Wu, Haihong Zhao, Wenhua Ling, Jun Wang, Yu-ming Chen, Tiannan Guo, Ju-Sheng Zheng. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. 2020.