Coronavirus update, 0020 GMT, 16 Mar

A tour inside the virus: Observations from sequencing all 30,000 letters in the virus from 512 patients

I last talked about this chart over a week ago. As you know, a lot changes in a week. The chart has almost doubled in complexity, thanks to the hard work, 24/7, of scientists from all over the world. Two things jump out at me, one a ‘fact,’ you can take to the bank, and one a ‘theory’ worth keeping our eyes on.

Before getting into the weeds here let’s review how to look at this chart.

First, if you are color blind you are going to need a color-reading friend to help you. Start with the map of the world. The colors are assigned as the location a patient was when the swab in the throat was taken and the virus was found. I wish they had stuck with the eight-crayon set I had in kindergarten instead of these beige tones but they have their reasons, I suspect. The bigger the circle, the more samples from that region.

Now the left side. Here is the genealogy, the family history of the coronavirus. While it reproduces without a mate, it still has new ‘generations’ going to the right in time, from Dec 2019 to Mar 2020. Every branch is a change in one letter in the 30,000 letters of the booklet entitled, ‘Instruction Manual for a Human Cell to Make a Coronavirus.’

By the way, since the typical book has about 1500 characters per page, this little horror story would be only 20 pages long! Not even Edgar Allen Poe could be so dark in so few pages! 🙂

The vast majority of these spelling errors don’t change the protein lego piece of the virus, which is where it interacts with the cell. Proteins are the action figures of life. The DNA/RNA are the instructions, which you follow, building your lego figures, until you have built your warrior, king, etc. and then you set the instructions aside. They truly are no fun!

If the DNA spelling error doesn’t change a lego piece in the protein, which is most of the time, it CANNOT, by the laws of biology, have a clinical impact on either the host or the virus. A few change the protein lego piece from one to another but, again, they are mostly, likely to have no clinical impact. They are just like those unique family ear, nose, toe, etc. (lego) shapes we all recognize at summer family reunions and picnics!

But now for two observations:

Observation One: Start at the first branch, what I have marked with a red and green arrow. The green arrow leads to 374 ‘children viruses,’ the red arrow leads to 138 ‘children viruses.’ So the ‘green virus’ has caused 73% of all of the cases anywhere in the world that have been sequenced. That’s a big difference.

When you follow the red arrow to the right and see where it’s children migrated to, you see the big, red cluster on the US. The second map shows the US up close with the bright red and ‘off red’ cases identified; here you see the Seattle epicenter as a big red dot.

When you search the top branch you see the occasional red dot, meaning in the US. But my estimate is that about three-fourths of all US cases can be traced to our ‘Patient Zero’ index case, a student who returned in mid-Jan from vacation in Wuhan to Seattle. One case in San Francisco is traced to him but it mostly stayed in WA state.

What does this mean? At this point the US cases are largely limited to the index case from China, and not from its largest concentration of active cases, Europe.

Second observation: this is raw speculation but it is important enough to keep in mind. Another cool feature of this chart on the website is that it tells you the exact page, line, and position of every letter change in the full 30,000 letter set. So you can see that, again an estimate, 80% of the cases make a change in the RNA which does not make a change in the lego piece in the protein it is the blueprint for. So by the rules of biology, these changes can NOT have a clinical significance. But the other 20% do change a single lego in the protein. While single lego piece protein changes are rare clinical events, two examples, sickle cell anemia and cystic fibrosis, involve a single lego piece change in the six billion letter human Book of Life which shows up a serious, life threatening diseases.

What if the higher rate of disease in Europe than in America and Australia is tied to a lego piece change in the proteins of this virus?

Only time will tell.

About Dr. Quay

Steven Quay is the CEO of Atossa Therapeutics Inc. (Nasdaq:ATOS), a clinical-stage biopharmaceutical company developing novel therapeutics for breast cancer and COVID-19. He received his M.D. and Ph.D. from The University of Michigan, was a postdoctoral fellow in the Chemistry Department at MIT with Nobel Laureate H. Gobind Khorana, a resident at the Harvard-MGH Hospital, and spent almost a decade on the faculty of Stanford University School of Medicine. A TEDx talk he delivered on breast cancer prevention has been viewed over 200,000 times. His 300+ contributions to medicine have been cited over 9,900 times, placing him in the top 1% of scientists worldwide. He holds 87 US patents and has invented seven FDA-approved pharmaceuticals which have helped over 80 million people.

The COVID-19 HOPE Clinical Trial​