Vincent Racaniello, a Columbia microbiology and immunology professor, writes about viruses, SARS-CoV-2, and related research, and hosts virology courses.
Commenters recommend Racaniello's free courses and lectures, and link his posts to explain viral mutation and variants.
1200 mutations away from RATG-13 is how significant exactly? I will propose that it is not particularly significant. One virus I work with, I have 14 variants ranging from 300 to 500 base-pair differences. That is from passing in a laboratory only. I have one variant that has a 14000 BP deletion! (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217056/#mmi144... TABLE S2) However, it is noteworthy for that reason. That said, these are dsDNA viruses with comparatively much slower mutation rates. 1200-base differences are almost nothing.
You're comparing apples and oranges. 14 mutational sites across a virus with 17k ssDNA genome is not comparable to RATG-13 vs SARS-2, which have not just 1200 mutations different, they're spread out over HUNDREDS of SNPs.
That's the important comparator. And why it will take so long to mutate one into the other by natural mutation rates.
>The two non-canonical arginines don't make it less likely?
Not particularly. CGG exists in MERS 15 times. NL63, 29 times. It even exists twice in a row in Human coronavirus 229E. Throughout all of the known alphacoronaviruses (94 described) CGG exists 1575 times. In betacoronaviruses, it exists more times than my processor can count without hanging, and I believe it tops out at 9,999 events.
I just ran blastn to figure that out. Using these datasets: https://www.ncbi.nlm.nih.gov/datasets/coronavirus/genomes/
Why is it so unlikely that synonymous mutational drift over the course of 70 years of infections…
I have chronic fatigue syndrome since a bad viral infection in 2001. I find this article quite unfortunate. There is plenty of good research being done into CFS that does not generate the outrage that the PACE trial has. There are many reasons that particular study has been the focus of campaigners while other researchers are encouraged or left in peace, but I would encourage those who are coming to this issue here for the first time to do some more reading before coming to an opinion.
The abstract to the study itself is here (the full study is behind Elsevier paywall):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633/?report=reader
David Tuller's blog critiquing the study is at:
http://virology.ws
Searching for "PACE trial" will bring up plenty of articles on either side of the debate.
My own thought as to why this particular study stirred so much controversy is that it has been seized on by some in the medical-political establishment in the UK as defining a solution for all CFS sufferers, and negating the need for further study into the condition (although recent hearings in UK Parliament have begun to reverse this approach), when really the effect demonstrated by the study is quite small. Fortunately, the US establishment has not taken this tack:
http://nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx
https://www.cdc.gov/me-cfs/index.html
CFS remains a poorly-understood disease with a grossly underfunded research program when the number of people affected…
...if you want to learn about the true beauty of viruses, learn about how they work, how their genetic code is written and "executed" to produce the simplest and smallest possible viable replicator (though not an independent replicator), grab a molecular virology textbook like [1] (it's not that hard - you can skim a more general molec bio book like [2], which is written in a style very friendly to all technically oriented people, including coders). Or check out a really cool virology blog - http://www.virology.ws/ (by one of the authors of book [1]), though latest posts are more about politics and social implications than cool basic science.
I have a feeling that von Newman would be extremely fascinated by modern molecular virology if he'd be alive today, considering his interest for minimal universal replicators [3]. If you think about it, modern computer science may very well owe its existence to von Newman's and Turing's interest in mathematical models of life itself!
(...if you want to learn more about the topic above, just google "von newman universal constructor" or "turing morphogenesis" or "schrodinger what is life" and start exploring, I don't want to spoil anyone's fun of finding out about this for yourselves :) )
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[1] http://astore.amazon.com/virologyws-20/detail/1555814433
[2] http://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/dp/0815341059/ref=sr_1_1?s=books&ie=UTF8&qid=1360312028&sr=1-1&keywords=Molecular+Biology+of+the+Cell
[3]…
Great overview of the biotech behind these COVID-19 nanobodies by Vincent Racaniello [1]:
> Human monoclonal antibodies that block infection with SARS-CoV-2 are being used to treat COVID-19 patients, but an alternative, antibodies produced in camelids (alpacas and llamas) might have advantages. Camelid monoclonal antibodies can be more cheaply produced in mass quantities in bacteria, and protein engineering can be quickly used to produce a better therapeutic product.
Nanobodies are small and stable enough to be delivered as a nasal spray unlike the current mabs (Regeneron and Eli Lilly) that are delivered intravenously.
The paper An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike [2] was discussed in the podcast TWiV 708: Alpaca llama full of nanobodies [3] on Jan 7th.
Unfortunately this spray is too late to impact the course of the current pandemic but it gives hope for the future.
[1] https://www.virology.ws/2021/01/14/camelids-for-covid/
[2] https://science.sciencemag.org/content/370/6523/1473
[3] https://www.microbe.tv/twiv/twiv-708/
I'm sorry to hear about your wife, that sounds awful. I also had post COVID issues, I couldn't get out of bed for a month and was very low energy for three. The doctors did nothing for me but luckily I have now recovered on my own. I tried eating lots of vegetables and lean meat (as per official nutritional recommendations) and it made me worse. I remember building up the strength every day just to chop the vegetables, eat and go back to bed. When I told my Doctor they dismissed it. I recovered on a diet of fatty red meat (1-2lb per day), milk, cream, eggs and fruit. The diet could be a timing coincidence but on the other hand maybe my Grandmother was on to something feeding me beef stew when I was ill as a kid.
There will be a law suit over how CFS patients are currently treated:
https://www.virology.ws/2020/07/15/trial-by-error-nice-on-exercise-and-post-covid-syndrome/
You might want to follow it. I will be.
He covered accident lab release in Question 4 [0]. He mentions that the WIV lab is well respected, well funded, well equipped, there was public logging of all relevant bat samples, along with parallel samples sent to other labs, lab workers were not the first who were sick, and there's genetic evidence that the virus did not originate in Wuhan.
Dr. Duehr links to a reference that talks about the cleavage site [1], which concluded that "Acquisition of the furin cleavage site might be viewed as a ‘gain of function’ that enabled a bat CoV to jump into humans and begin its current epidemic spread"
[0] https://old.reddit.com/r/science/comments/gk6y95/covid19_did_not_come_from_the_wuhan_institute_of/fqpccr1/
[1] https://www.virology.ws/2020/02/13/furin-cleavage-site-in-the-sars-cov-2-coronavirus-glycoprotein/