Some news on the variants of SARS-CoV-2 and the effectiveness of the Pfizer vaccine, (good news)!

[NNadir]

Today at the virtual ACS meeting I attended two lectures, one by Phil Dormitzer of Pfizer and one from Melissa Moore of Moderna.

I don't have much time to discuss the details, but during Dr. Dormitzer's fascinating lecture some cool things came up.

It appears that the variants are fairly well removed from the target areas of the vaccines, which a good thing. They have nonetheless been completely mapped, and work is underway to address them if needed. In Dr. Dormitzer's lecture he specified them, if my notes are correct as D614G (Aspartic Acid replaced at the 614th residue of the spike protein by glycine), N501Y, replacement of asparagine at the 501st residue by tyrosine, and E484K, replacement of glutamic acid at the 484th residue by lysine.

There are some genetic differences between races in diseases and response to diseases; for example, women of Chinese origins are much less likely than women of European extraction to get certain forms of breast cancer because of a variant in the COMT gene (catechol O methyl transferase). African American men and women are less likely to respond to certain blood pressure medicines, (which makes it regrettable that omipatrilat was not approved, since it treated this hole in medicine.)

It turns out that African Americans are winners in terms of the ethnic profile of the Pfizer vaccine effectiveness. For them, according to the data shown in the talk and them alone, the Pfizer vaccine is 100% effective in preventing Covid infections.

Dr. Moore's lecture made me realize something that had not occurred to me in the development of these novel RNA drugs and vaccines. (I'm not a nucleic acid kind of guy.) They are a lot more difficult to make than one might think niavely. This is because of the multiplicity of codons for several amino acids. One has to be very careful in considering the availability of transfer RNA's corresponding to these codons, since they are not necessarily available in the same concentrations in organisms in which they are generated. Dr. Moore pointed out that for the SARS-Cov-2 Moderna vaccine there were actually 10^201 choices that could have been made in the codon sequence, which is a number larger than all of the atoms in the known universe! She briefly described the statistical methods used to manage this chemical space and make wise choices.

Nevertheless, Moderna has spent years learning how to choose the particular sequences of codons, and they are also ready to make changes FAST! FAST! FAST! as necessary.

Another thing: Both vaccines incur, according to the existing clinical trial data, a higher level of immunity than one actually obtains by having Covid. This suggests that even people who have had Covid might want to consider vaccination.

Very cool, very cool.

[intrepidity]

1. KnR nt

[soothsayer]

2. Excellent

[mucifer]

3. Wonderful! Just one thing. In the end of your post you discuss people who have had covid and

that they should have the vaccine. Many people who have had covid were asymptomatic. So I would think a lot of people who are currently being vaccinated do not consider themselves to have had covid because they never had symptoms and they don't know they had it.

[NNadir]

4. This is true. In that case, it doesn't hurt. I have had both Moderna injections. When I...

...donate blood, they (the Red Cross) claims they will notify you if you have antibodies. I donated recently, after the second dose. I haven't heard from them, but I really didn't expect that I would.

[central scrutinizer]

5. My BIL was sick with covid for about 10 days back in December.

He’s getting the two Pfizer shot regimen anyway.

[Claire Oh Nette]

14. Same

I think I felt first COVID symptoms a day or two after Pfizer announced application for approval in December. Three really rough weeks.

Got second pfizer dose yesterday. Some chills and sweats last night, about 15 hours after injection. No fever, though. Nurse at the clinic site said full immunity after seven days; takes 14 for Moderna.

COVID immunity ~ 90 days. So far, vaccine immunity for both double dose vaccines is 6 months, so far. This needs to get out, everywhere.

People choosing not to take the vaccine, who minimized its severity out of fear, who didn't want to mask, who didn't want to be inconvenienced in any way, are selfish pricks.

[wnylib]

18. So do we need to get a booster in 6 months?

[Claire Oh Nette]

20. Not that I know of...

We're likely six months out from the first vaccines in actual people. Phase IV post market studies will be ongoing by all the vaccine companies. I've not read anything indicating we need a booster, although I'm afraid we'll have some variant of this coronavirus to contend with in the future because we have Evangelical Whites and Republican males who refuse vaccines, thus allowing mutations.

I get a flu shot every year, and I'm due for my shingles vaccine and my pneumonia booster. This should not be political at all, but the former guy made it political. He was afraid of it, so he minimized it publicly to reassure himself it was harmless, knowing it wasn't. Wearing a mask is what nurses do, apparently and nurses are women, so it made him look less masculine and tough to his base.

And, now that we're finally getting vaccinated, and things are opening up, the mask holes are going to cause a ruckus when they aren't allowed in because they can't provide proof of vaccine to take cruises, board airplanes, attend concerts...

Tell the next person who won't get vaccinated you'd like to hang out at their house while you recover from covid. The cough. See how quick they back up. Unconscionable selfishness and refusal to acknowledge science. Alternative facts are lies. Their politics are wrong, and they're just shocked that we're going to call them out on their uninformed, selfish positions.

PS private companies and private businesses want this. Businesses want this. I'd wager 75% of *Americans* want this, too. Americans.

[wnylib]

21. The first vaccinations started in December,

so we're about 4 months into vaccination for them. Maybe more like 3 months because the shots did not start at the beginning of December and were so limited that few people got them.

The UK mutation is the dominant form of the virus in the US now. It is more contagious and causes more serious illness. By July, the 6 month vaccine immunity will be over for people who got the vaccine first. Those people will be vulnerable again and I doubt that the viral mutations will be gone by that time.

If the South African strain spreads in the US, we will have hospitalizations and rising deaths again. We will need a booster, I think. Moderna is working on one that works on the South African version better. I hope that by the time they have it, we don't have an even newer mutation.

In other words, the current vaccinations help and I am glad to be getting my second shot on Friday. But the virus will still be around for a while.

[SheltieLover]

6. K&R!

Ty!

[Staph]

7. Have you read The Code Breaker, by Walter Isaacson?

It's the story of Jennifer Doudna and her decades-long quest to understand RNA and then to figure out how to use RNA to prevent and treat a wealth of diseases.

The book has a lot of science details, but written to be understandable by those of us who haven't studied any serious science since high school. The last chapters deal with the COVID-19 pandemic and the search for operational tests, vaccines, and treatments, as well as Doudna's Nobel Prize.

[NNadir]

11. No, I'm afraid I haven't read it, but I am familiar with her work of course.

CRISPR will change the world, mostly, one hopes, for good.

[ancianita]

23. I highly recommend it.

An amazing story for all of us non-scientists, all the more reason for everyone to read it.

The biotech sciences just might move ahead of technology in changing the future of humanity.

[eppur_se_muova]

16. Thanks for the book rec. I would have assumed from the title that is was about cryptanalysis! nt

[Goonch]

8. ;-{)

[Karadeniz]

12. I wonder why that last eta in Hellenica has an accent..... love ancient Greek!

[PaulnFortWorth]

15. It Looks Cool But...

What does it mean?

[Goonch]

19. It's Greek To Me

[wackadoo wabbit]

9. If you have the time, I'd love to hear more about the COMT gene info that you learned

I'm homozygous for a rare allele on the COMT gene; and, while I know it has implications on many fronts, I hadn't heard that this gene can affect cancer susceptibility/resistance as well. What allele did the Chinese-origin women have?

Thank you for the ACS meeting updates. I've been reading them with great interest.

[NNadir]

10. I'm afraid it was a long time ago that I considered this question in connection with certain...

...analytical technology, specifically an LC/MS/MS analytical method for tracing estrogen metabolites. If I recall correctly, it involved a single nucleotide polymorphism, but I'm an old guy and I don't remember where or what specifically it was.

If I recall correctly the issue was with the oxidation of 1,2-diol species, specifically 2-hydroxyestradiol, and 2-hydroxyestrone to give quinones that form DNA adducts, leading to cancer by fitting into the minor groove of DNA in such a way to facilitate adduct formation.

I do know that there was one clinical trial of 2-methoxyextradiol as an anti-cancer therapeutic, but I don't think it went anywhere.

It was a long time ago.

How is it that you know about this allele?

[wackadoo wabbit]

22. Thanks for the info

Actually, after posting I went onto PubMed to see if the paper had been published. There are actually a couple of interesting papers on this topic that I'm going to delve into, so thank you for bringing it to my attention! I honestly had no idea.

I first became aware of the COMT gene when I was tracking down a cause for some symptoms (quirks?) that I have. They seemed to be associated with a less-than-optimal functioning of the COMT enzyme, which is, of course, encoded by the COMT gene.

So, to test my theory, I asked my neurologist to test my COMT gene for its alleles, which is how I discovered that I'm homozygous for an allele that causes markedly decreased COMT activity.

What this means is that, despite the many downsides of having a poorly functioning COMT gene, I've got more dopamine, so I guess it's all good.

[NNadir]

24. That's interesting. Based on what I know...

...without knowing whether you are male or female, and without particular medical expertise, if you are the latter, or even the former, I would be careful about monitoring yourself for potential neoplasms.

Steroids are fairly planar, and as such can be carcinogens very much like PAHs, again, insertion in the minor groove followed by adduct formation. These adducts are well known and have been detected by various means.

It sounds as if you have the sophistication to understand this, since I know very few people who even think about their COMT status, so I'm sure you'll be cognizant of what's involved.

Good luck!

[IbogaProject]

13. Chemistry conferences are great

Chemistry conferences are great learning experiences !!

[eppur_se_muova]

17. I hope that info about AA immunity gets into the M$M quickly ....

for reasons of deeply regrettable history, AAs are among the most resistant demographics to vaccination.

Maybe you could write to Rachel.

[NNadir]

25. I'm not entirely sure if vaccine resistance among any person is necessarily connected...

...with efficacy so much as culture, and these cultural factors may differ from one ethnic group to another, but the effect is the same.

As it happens, most of the anti-vax people I know are white, and there's no talking to them or getting it through their thick heads.

There are, in all ethnic groups, people who simply reject science.

Our Trump worshiping white racists are certainly not going to be moved by efficacy, particularly since they believe Covid isn't real.

The good news is that African American people who are vaccinated, at least with the Pfizer vaccine, will not get Covid, if the data I saw yesterday holds up. Given the inequity of access to health care, we can be glad that this at least is some consolation.

I have always regarded the rejection of omapatrilat by the FDA as a blow against African Americans, who as a population, for whatever reason, are less responsive to other blood pressure medicines. I think with personalized medicine approaches, identifying a biomarker for the angioedema that killed that drug, it might have been approved in modern times.

[Sucha NastyWoman]

26. Do antivaxers with high blood pressure turn down high blood pressure medicine?

I can’t imagine how they think

[FakeNoose]

27. K & R Thanks!

[speak easy]

28. 'African Americans are winners'

I can not hear this enough. Got that knee off the neck, then stand back!

[NNadir]

29. Well, in this case, according to the trial results, any African American who gets the Pfizer...

....vaccine can breathe easier.

Given history, it some small consolation.