I found I had more to say about Spike biochemistry, so here it is… Well, here the first part is. More to come tI found I had more to say about Spike biochemistry and I want to help bridge the gap between the goofy and the serious and help people understand things like protein domain architecture figures and some jargon, so here it is… Well, here the first part is. More to come tomorrow. 



The Spike protein is kinda like a molecular Transformer. It latches onto the cell’s angiotensin-converting enzyme 2 (ACE2) receptor, gets cleaved by cellular proteases (protein cutters) and then undergoes a major shape-shift (aka conformational change). This transformation from the “pre-fusion conformation” to the “post-fusion conformation” is kinda like snipping the string tying something  – it releases structural constraints so S can extend parts of itself that were previously hidden called fusion peptides, which “attack” the cellular membrane and pull it towards the viral one, getting them to fuse & allowing the virus to spill out its guts inside of our cells and hijack our cellular machinery to do its bidding. ⠀

Just learning more about this process from a “basic science” perspective would be fascinating in and of itself, but there’s also “translational science” value (putting the knowledge to direct use). The best way to prevent a person from getting the disease Covid-19 is to prevent them from coming into contact with SARS-CoV-2, the novel coronavirus that causes it (this is why we’re doing all this social distancing stuff). But if the virus gets into someone’s body, it still has to get inside their cells. If you could block the Spike protein from binding and/or shape-shifting (such as with neutralizing antibodies) you could prevent the virus from getting in. For this reason, S has been of great interest for the development of vaccines (get someone’s body to produce their own such antibodies prior to real exposure) and therapeutic antibodies (give infected people pre-made antibodies to help prevent the virus from infecting more cells). ⠀

So let’s take a look at this awesome protein at the structural level 

For more information about Spike (and figures), see this past post: https://bit.ly/coronavirusspike  

For more information about proline stabilization of Spike, see https://bit.ly/prolineperforms; video on YouTube: https://youtu.be/chScI8lPpAE  

Here’s the info for the papers whose structures I showed you:

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation 

BY DANIEL WRAPP, NIANSHUANG WANG, KIZZMEKIA S. CORBETT, JORY A. GOLDSMITH, CHING-LIN HSIEH, OLUBUKOLA ABIONA, BARNEY S. GRAHAM, JASON S. MCLELLAN 

SCIENCE13 MAR 2020 : 1260-1263 https://science.sciencemag.org/content/367/6483/1260

Distinct conformational states of SARS-CoV-2 spike protein BY YONGFEI CAI, JUN ZHANG, TIANSHU XIAO, HANQIN PENG, SARAH M. STERLING, RICHARD M. WALSH JR., SHAUN RAWSON, SOPHIA RITS-VOLLOCH, BING CHEN 

SCIENCE25 SEP 2020 : 1586-1592 

https://science.sciencemag.org/content/369/6511/1586

more Covid-19 resources: https://bit.ly/covid19bbresources


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