Nature: How the coronavirus infects cells--and why Delta is so dangerous

[intrepidity]

Link to tweet

The virus that causes SARS, SARS-CoV, uses either of two host protease enzymes to break in: TMPRSS2 (pronounced ‘tempress two’) or cathepsin L. TMPRSS2 is the faster route in, but SARS-CoV often enters instead through an endosome — a lipid-surrounded bubble — which relies on cathepsin L. When virions enter cells by this route, however, antiviral proteins can trap them.

SARS-CoV-2 differs from SARS-CoV because it efficiently uses TMPRSS2, an enzyme found in high amounts on the outside of respiratory cells. First, TMPRSS2 cuts a site on the spike’s S2 subunit8. That cut exposes a run of hydrophobic amino acids that rapidly buries itself in the closest membrane — that of the host cell. Next, the extended spike folds back onto itself, like a zipper, forcing the viral and cell membranes to fuse.

The virus then ejects its genome directly into the cell. By invading in this spring-loaded manner, SARS-CoV-2 infects faster than SARS-CoV and avoids being trapped in endosomes, according to work published in April by Barclay and her colleagues at Imperial College London9.

The virus’s speedy entry using TMPRSS2 explains why the malaria drug chloroquine didn’t work in clinical trials as a COVID-19 treatment, despite early promising studies in the lab10. Those turned out to have used cells that rely exclusively on cathepsins for endosomal entry. “When the virus transmits and replicates in the human airway, it doesn’t use endosomes, so chloroquine, which is an endosomal disrupting drug, is not effective in real life,” says Barclay.

Much more at https://www.nature.com/articles/d41586-021-02039-y

[roamer65]

1. K&R

[Blecht]

2. Nature .... pfft

I wanna wait to hear what Tucker Carlson has to say!

[JudyM]

3. K&R

Interesting.

[Moostache]

4. I am baffled that people believe YouTube and Facebook over that level of research and detail

It is truly stunning that the pace of discovery and publishing SARS-COV-2 data has been so extraordinary and yet so many people are stuck in disinformation campaigns and conspiracy theory hell holes.

[scipan]

5. Holy cow. Are we sure the devil didn't create this?

I'm an atheist, I'm kidding, and humble enough that I'm not gonna get in front of scientists. But geez:

First, some of the newly made viral spike proteins travel to the surface of the cell and poke out of the host-cell membrane. There, they activate a host calcium-ion channel, which expels a fatty coating onto the outside of the cell — the same coating found on cells that naturally fuse together, such as muscle cells. At this point, the infected cell fuses to neighbouring cells expressing ACE2, developing into massive individual respiratory cells filled with up to 20 nuclei.

These fused structures, called syncytia, are induced by viral infections such as HIV and herpes simplex virus, but not by the SARS virus,

[intrepidity]

6. If you throw enough spaghetti at the wall,

eventually *something* is gonna stick.

That's viral natural selection, in a nutshell

The key to defense is not allowing *any* spaghetti to be tossed at the wall. But that requires serious efforts to prevent infections and thus opportunities for the virus to mutate.

[scipan]

8. It's amazing. An example of convergent evolution.

[dalton99a]

7. Kick