Proteolytic Processing of Coronavirus Fusion Proteins

Many viruses come out from the host cell as complete but inactive particles. A common mechanism to activate the virus is to cut the protein spikes on the particle surface with a proteolytic enzyme like trypsin. This happens for example to influenza virus particles. It also happens to a Coronavirus called Porcine Epidemic Diarrhea Coronavirus or PEDV. The precise timing of the “proteolytic attack” seems to be uncertain and could happen in different stages of the virus maturation. On the left side of the illustration below, the baby virus is assembled and exits the cell with stable spike proteins. Proteolytic enzymes cut the spikes in certain places, leading to a destabilized but active virus. With the activated spikes, the virus is ready to bind and enter a new host cell. There, it again hijacks the protein production machinery and starts producing new virus particles.

Proteolytic processing of coronavirus fusion proteins
As you can guess from the virus name, infected pigs gets diarrhea and dehydration. For young piglets, the infection is many times deadly. By understanding the virus entry mechanism better, new ways to stop the virus could be invented. And that is what my friend O.W. has been working on for the past few years. In a recent publication, he addressed the timing of the spike activation among other topics, and it seems that it could be in fact taking place after the receptor binding and not before, like my photo-realistic drawing shows (Wicht O. et. al. Proteolytic activation of the porcine epidemic diarrhea coronavirus spike fusion protein by trypsin in cell culture. 2014. J Virol. 15;88(14):7952-6). This publication is one of the studies in O.W’s PhD thesis “Proteolytic Processing of Coronavirus Fusion Proteins” and the drawing here is the cover illustration for the book.

book pic

Congrats to O.W. for the PhD degree and thanks for this fun project!

I put up the drawing also to my society6 page. Check it out here.

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