Thread by @EricTopol, Nature can be beautiful but also evil.It has brought us the worst [...]

Nature can be beautiful but also evil.
It has brought us the worst pandemic in more than 100 years.
What is it about #SARSCoV2 that makes it so nefarious? 1/

As compared with SARS, this virus has a furin polybase site that when cleaved gives it enhanced tropism 2/x
https://www.nature.com/articles/s41591-020-0820-9.pdf @K_G_Andersen @NatureMedicine
https://science.sciencemag.org/content/369/6503/510 @ScienceMagazine

This tropism translates to its ability to bind ACE2 wherever it is expressed in the body 3/x
https://embopress.org/doi/10.15252/msb.20209610…
@MolSystBiol
A brilliant synthesis of pan-body data, by
@DrLindskog
and colleagues
@UU_University

That can lead to pan-body involvement is what was originally labelled a "respiratory virus." Even presentations such as stroke or heart attack, without respiratory signs, have been encountered 4/x

The body's innate immunity relies in part on interferons. But of course this virus has a way to take that defense down
https://www.nature.com/articles/s41423-020-0514-8 5/x

SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70

https://www.nature.com/articles/s41423-020-0514-8

Beyond the pan-body potential involvement, there is the full spectrum from no symptoms to lethality. That happens with other viruses, but the proportion of people without symptoms (or not discernible) is quite high, 30-40%. 6/x

Many of the people without symptoms don't know they are taking internal hits, such as lung CT abnormalities. So they are both silent infectors and silent infectees. 7/x

Then there's the chronic, enduring, debilitating symptoms for what is now known as #LongCovid (aka long haulers) for which there's still much more to learn, but all of that was just reviewed by @jcouzin @ScienceMagazine 8/x
https://www.sciencemag.org/news/2020/07/brain-fog-heart-damage-covid-19-s-lingering-problems-alarm-scientists

So when you add a virus that can attack pan-body, leave many people without symptoms, lead to chronic symptoms in many, and death in ~0.5-6%, that's pretty bad.
The only good thing about this virus is that it is only very slowly evolving, making it well suited for a vaccine 9/x

Potent neutralizing antibodies (in clinical trials)are the best short term approach to treat the virus. But there's a catch. Escape variants may render them ineffective. So even a cocktail approach of multiple monoclonals is being pursued 10/x https://science.sciencemag.org/content/early/2020/06/15/science.abd0831

Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual...

Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate...

https://science.sciencemag.org/content/early/2020/06/15/science.abd0831

All these distinctive features of #SARSCoV2 make it a formidable foe. But the science is taking it on, it's moving fast, and I'm convinced in the months ahead we'll see further lowering of the fatality rate, understand the immune response better, and ultimately prevail. 11/f

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