[Pestilence] https://youhavetoliveyour.life/

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

(Thread IKs: PoundSand)

Pingui: Jun 4, 2006; WTF?

Another cool piece by Haseltine about the folly of merely looking at antibody reactions to BA.2.86 (in full, with all the bells and whistles, but no highlights, as I quite enjoy the article in full and it is a good primer on why JN.1/BA.2.86* is worth paying attention to):
"JN.1: The Odd Man Out Among Omicron Sublineages (Updated)"

https://www.forbes.com/sites/williamhaseltine/2023/10/26/jn1-the-odd-man-out-among-omicron-sublineages/ posted:

A new Covid-19 variant demonstrates the rapid adaptability of the SARS-CoV-2 virus. This latest emerging SARS-CoV-2 variant, JN.1, was identified in Luxembourg on August 25, 2023, followed by England, Iceland, France, and the United States. In the GISAID SARS-CoV-2 database, there are 91 instances of JN.1 at the time of writing, suggesting that many hundreds, if not thousands have been infected with the variant as sequencing efforts have been largely halted.

What is most intriguing about JN.1 and why I believe there is cause for concern is the striking amount of differences between it and the leading viruses today: XBB.1.5 and HV.1. The XBB.1.5 variant is the target of the latest vaccine boosters in the United States. Most emerging variants are descendants of this virus. HV.1 is a relative newcomer and boasts a few differences from XBB.1.5 but is mainly similar to XBB.1.5.

To quantify the departure of JN.1 from these viruses, there are ten additional unique mutations in HV.1 compared to XBB.1.5, or a difference of about 12%. JN.1 contains 41 additional unique mutations compared to XBB.1.5, or 40%. Most of the changes in JN.1 are found in the spike protein, which likely correlates to increases in infectivity and immune evasion.

Recent investigations suggest that the BA.2.86 variant, the phylogenetic parent to JN.1, is possibly a recombinant of earlier BA.2 Omicron sublineages and later XBB lineages. This would explain why there are several similarities to XBB.1.5, but also a distinct number of differences, both within and outside the spike protein.

_{FIGURE 1: SARS-CoV-2 lineage map. Note the emergence of JN.1 and others from BA.2.86.}

Many spike protein mutations are among those we have seen in previous variants of concern, such as E484K and P681R, which were first identified in the Alpha and Beta variants of SARS-CoV-2 in early 2021. Why those mutations fell out of circulation in the Omicron family of variants is unclear, but their reemergence in JN.1 is noteworthy.

What catches my attention about JN.1 is not the reemerging mutations from earlier variants but the novelty of select mutations in the spike protein. Several of these mutations have only been sequenced a few thousand times from a database of over 16 million samples throughout the pandemic. None, however, are unique to JN.1.

In the N-terminal domain, which plays a role in virus entry post-infection, mutations such as R21T, S50L, V127F, R158G, and others may improve viral entry efficiency, as well as immune escape from antibodies by implementing N-glycosylation sites.

In the receptor-binding domain, we observe a similar phenomenon. V445H, S450D, and L452W have all been sequenced less than two thousand times, among other rare mutations, all of which could work to improve ACE2 binding affinity or reduce antibody binding efficiency.

_{FIGURE 2: Spike protein mutational profile of JN.1 compared to XBB.1.5 and HV.1.}

I want to draw your attention to mutations outside the spike region, which may significantly affect the virus's pathogenicity and spread. Throughout the genome, there are a wide variety of mutations in the Orf1ab replication-transcription complex (NSP1-16), some in the structural proteins (E, M, and N), and a few in the accessory proteins (Orf3a-8). We bring attention to these because mutations in some of these proteins, particularly the N protein, can make a significant difference in virus replication.

Below is the entire catalog of mutations found throughout the virus.

_{FIGURE 3: JN.1 nonspike mutations}

_{FIGURE 4: Nonspike protein mutational profile of JN.1 compared to XBB.1.5 and HV.1.}

A nonspike protein that is heavily mutated in JN.1 is the NSP3 protein. There are six mutations in NSP3, namely T24I, V238L, G489S, K1155R, N1708S, and A1892T. NSP3 is one of the most active proteins in the virus, playing roles in viral RNA binding, polyprotein processing, and other functions. While the exact function of these mutations is unknown, they are likely to increase the efficiency of many of these mechanisms, creating a more functional and pathogenetic virus.

I also note the heavily mutated N protein. The mutations R203K and G204R have been mutated in most virus variants throughout the pandemic and likely improve viral replication rate. The other mutations in N may also work to improve viral replication.

While the Orf8 protein is truncated in the widespread XBB.1.5 variant, it is fully present in JN.1.

There are several explanations for the mutations within and particularly outside of the spike protein. The first is adaptation to more aggressive infectivity. The second is to escape from neutralizing antibodies. The third is adaptation to more efficient post-infection pathogenesis, including replication aided by mutations in the N protein. The fourth is immune evasion from T cell recognition. Dr. Gaurav Gaiha and colleagues identified early in the pandemic that some mutations reduced binding affinity to T cell epitopes. In JN.1, eight mutations added from the XBB profile are among those Gaiha identifies, suggesting they have been counterselected for T cell recognition.

I also note the presence of synonymous mutations or those that do not result in an amino acid change. There are likely several synonymous mutations littered throughout JN.1; however, collecting data on these mutations is much more complex than amino acid mutations.

While synonymous mutations do not impact the amino acid sequence of the virus, it does affect the tertiary structure of the virus�s RNA, which studies suggest can play a role in the adaptation of the virus to the human host environment. They may also play a role in the relative abundance of viral encoded protein and immune responses in the infected person.

For instance, a recent study on the SARS-CoV-2 N protein shows that the N-terminal domain of N recognizes and binds RNA sequences in the five prime untranslated regions of the virus. The N protein is involved in RNA transcription and genome packaging into virus particles, which play a crucial role in virus transmission. Thus, altering the structures of the five prime ends could impact the function and efficiency of N, impacting the overall viral function of SARS-CoV-2.

My colleagues and I will soon release a book on molecular biology concerning the SARS-CoV-2 virus (Patarca and Haseltine, to be published by Wolters Kluwer in 2024). In the book, we discuss the role of each protein in the pathogenesis of Covid-19. Over time, and with further advances in artificial intelligence technologies, we will better understand the impact of intricate mutations on protein function. The slightest change can have a massive impact on the protein structure and the tertiary structure of nucleotide sequences. Eventually, we will be able to predict the pathogenesis of a virus before it infects a host.

In recent days, data on the pathogenicity of JN.1 was released. Dr. David Ho and colleagues from Columbia University reported that BA.2.86, the parent of JN.1, has a remarkably high affinity for the ACE2 receptor, suggesting a highly efficient transmissibility, which was more than likely passed down to JN.1.

Further, Dr. Yunlong Cao and colleagues from Peking University characterized the JN.1 variant in pathogenetic detail, showing a weakened neutralizing antibody response compared to the more common XBB.1.5 variant.

_{FIGURE 5: Weakened neutralizing antibody response to JN.1.}

Cao and colleagues attribute the more efficient immune evasion to the spike mutation L455S, which reduces the binding efficiency of class 1 monoclonal antibodies.

It remains to be seen whether JN.1 will cause a new wave of Covid cases akin to Alpha or Omicron in years past. With only 91 recorded instances of JN.1, this will likely be one of many variants throughout the pandemic to appear disconcerting but remain relatively minor. If GISAID data correlates to global cases, it seems JN.1 is beginning to slow down and plateau compared to earlier this month.

It is crucial to be aware of these threats before they become widespread, not after. As we enter the winter months, another wave of cases could likely occur, and JN.1 is an avenue for that to take place.

Link to last piece I posted from Haseltine which was also very good:

Pingui posted:

"Covid-19: The Shapeshifting Protean Virus"

# ? Oct 28, 2023 12:56

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# ? May 23, 2024 03:23

Mola Yam: Jun 18, 2004; Kali Ma Shakti de!

M1.LD

# ? Oct 28, 2023 13:07

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

Mola Yam posted:

M1.LD

# ? Oct 28, 2023 13:08

Gunshow Poophole: Sep 14, 2008; OMBUDSMAN
POSTERS LOCAL 42069; Clapping Larry

*pounding table*

orf8! orf8!

# ? Oct 28, 2023 14:17

genericnick: Dec 26, 2012

Lmao, did the cryptid shitter move to one of the Austrian states?

# ? Oct 28, 2023 14:29

Strep Vote: May 5, 2004; أنا أحب حليب الشوكولاتة

quote:

My colleagues and I will soon release a book on molecular biology concerning the SARS-CoV-2 virus (Patarca and Haseltine, to be published by Wolters Kluwer in 2024)

Get ready for new thread required reading.

# ? Oct 28, 2023 15:04

Bruce Hussein Daddy: Dec 26, 2005; I testify that there is none worthy of worship except God and I testify that Muhammad is the Messenger of God

Shoutout to the goon at the Furman game today.

# ? Oct 28, 2023 20:49

sonatinas: Apr 15, 2003; Seattle Karate Vs. L.A. Karate

kid had a super faint antigen line, could see it with magnifier so tried to schedule PCR for myself(negative antigen but under weather) and my kid at Walgreens.

after scheduling it and arriving they told me they don�t do it anymore and should go to urgent care down the street.

so thankfully the urgent care place said they do PCRs and now in waiting room. however I have a strong feeling they gonna say oh it�s antigen because people don�t loving know anything� we will see.

we got the tools

# ? Oct 28, 2023 21:09

Pingui: Jun 4, 2006; WTF?

Which one of you...

https://wreg.com/news/local/suspects-rob-abc-delivery-driver-steal-covid-supplies/ posted:

Suspects rob ABC delivery driver, steal COVID supplies

# ? Oct 28, 2023 21:49

sonatinas: Apr 15, 2003; Seattle Karate Vs. L.A. Karate

sonatinas posted:

however I have a strong feeling they gonna say oh it�s antigen because people don�t loving know anything� we will see.

we got the tools

lol I was right. they only have antigen and PCR is $3k.

of course the front desk people know jack poo poo

# ? Oct 28, 2023 22:02

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

sonatinas posted:

lol I was right. they only have antigen and PCR is $3k.

gl with everything, goon

# ? Oct 28, 2023 22:05

Pingui: Jun 4, 2006; WTF?

Only source I can find, but Charlotte Klein is media reporter at Vanity Fair and this is her Twitter profile, so maybe.
https://twitter.com/charlottetklein/status/1717549688092537046

# ? Oct 28, 2023 22:06

SardonicTyrant: Feb 26, 2016; BTICH IM A NEWT
熱くなれ夢みた明日を
必ずいつかつかまえる
走り出せ振り向くことなく
&

sonatinas posted:

lol I was right. they only have antigen and PCR is $3k.

of course the front desk people know jack poo poo

It's the natural result of making everything into a service job; cut corners everywhere. No one knows anything anymore.

# ? Oct 28, 2023 22:08

Wrex Ruckus: Aug 24, 2015

Pingui posted:

Only source I can find, but Charlotte Klein is media reporter at Vanity Fair and this is her Twitter profile, so maybe.
https://twitter.com/charlottetklein/status/1717549688092537046

would this be his second or third tour?

Wrex Ruckus has issued a correction as of 22:11 on Oct 28, 2023

# ? Oct 28, 2023 22:08

Pingui: Jun 4, 2006; WTF?

sonatinas posted:

(..)
PCR is $3k.
(..)

lmao at this, fingers crossed it was a false positive.

# ? Oct 28, 2023 22:08

sonatinas: Apr 15, 2003; Seattle Karate Vs. L.A. Karate

Pingui posted:

lmao at this, fingers crossed it was a false positive.

me too. ain�t paying 3k.

what a world

# ? Oct 28, 2023 22:09

Pingui: Jun 4, 2006; WTF?

Wrex Ruckus posted:

would this be his second or third tour?

If it is real and this is the standard level of communication about it, we have literally no idea.

Pingui has issued a correction as of 22:20 on Oct 28, 2023

# ? Oct 28, 2023 22:10

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

$3k per PCR is "buy your own equipment and reagents and run the tests yourself" territory.

Or just get a fuckton of Cue tests I guess.

# ? Oct 28, 2023 22:15

The Oldest Man: Jul 28, 2003

Pingui posted:

Only source I can find, but Charlotte Klein is media reporter at Vanity Fair and this is her Twitter profile, so maybe.
https://twitter.com/charlottetklein/status/1717549688092537046

That's a full lmao from me

# ? Oct 28, 2023 22:15

ex post facho: Oct 25, 2007

Got my flu and Moderna booster in different arms same day earlier this week. Definitely wasn't as bad as the previous 4 though I did get full body chills that night and some sleepiness the next day. I took a couple ibuprofen and started feeling OK pretty soon after though

# ? Oct 28, 2023 22:18

Psycho Society: Oct 21, 2010

drat the top infectious diseaze guy seems pretty bad at even preventing infection to his own person. maybe he actually sucks at it?

# ? Oct 28, 2023 22:20

sonatinas: Apr 15, 2003; Seattle Karate Vs. L.A. Karate

Zugzwang posted:

$3k per PCR is "buy your own equipment and reagents and run the tests yourself" territory.

Or just get a fuckton of Cue tests I guess.

so I asked the nurse who came in after the tech told me 3k and she said it�s actually around $100 if insurance denies it so I said yes and fingers crossed.

cool health care system here to just be completely confusing

at least the nurse was in an enviromask

# ? Oct 28, 2023 22:27

maxwellhill: Jan 5, 2022

Pingui posted:

Which one of you...

we gotta do something about all these suspects!

# ? Oct 28, 2023 22:43

Platystemon: Feb 13, 2012; BREADS

Pingui posted:

Only source I can find, but Charlotte Klein is media reporter at Vanity Fair and this is her Twitter profile, so maybe.
https://twitter.com/charlottetklein/status/1717549688092537046

# ? Oct 28, 2023 22:47

Rescue Toaster: Mar 13, 2003

He gets two because his means tested way better.

# ? Oct 28, 2023 23:15

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

How inconsiderate of Fauci to use up all the pax like this

# ? Oct 28, 2023 23:24

Skinnymansbeerbelly: Apr 1, 2010

I don't know if I'm maybe just thread poisoned or what but I think the director of When Evil Lurks has some opinions about COVID & society.

# ? Oct 28, 2023 23:41

icantfindaname: Jul 1, 2008

sonatinas posted:

lol I was right. they only have antigen and PCR is $3k.

of course the front desk people know jack poo poo

Jesus, what country is this?

# ? Oct 28, 2023 23:55

Why Am I So Tired: Sep 28, 2021

Hey, just a heads up to anyone on Apple Health who's trying to get Novavax - call the pharmacy ahead of time and ask the pharmacist to submit a test claim so you don't waste your time / stand in a cloud of disease for no reason. They just ran one for us (after we got rejected in person earlier in the week for another insurance error) and they (insurance) are rejecting Novavax but not Pfizer or Moderna, even though they directly told us Novavax would be covered. The pharmacy is also in-network.

We have the tools and it's our fault if we die :911:

# ? Oct 28, 2023 23:56

kazmeyer: Jul 26, 2001; 'Cause we're the good guys.

maxwellhill posted:

Don't sleep on home ventilation, y'all. I thought that I wasn't sleeping on it and I still was. Got out a CO2 monitor in my new place, I guess I've never charged it up here, and it immediately started alarming 1600+.

I got an Aranet figuring I'd use it out and about to monitor ventilation, and it instead taught me how lovely the ventilation was in my own apartment. First night in the new place I slept with my bedroom doors shut and woke up to over 2000. Now I keep better airflow, the deck door cracked open, and throw the bedroom windows open at least once a day to change out the air. And I feel leagues better for it, too.

# ? Oct 28, 2023 23:57

Zugzwang: Jan 2, 2005; You have a kind of sick desperation in your laugh.; Ramrod XTreme

icantfindaname posted:

Jesus, what country is this?

This would be an ace thread title if the current one wasn't already so good

# ? Oct 28, 2023 23:57

Platystemon: Feb 13, 2012; BREADS

itt goons discover the value of well-ventilated indoor spaces

but like, through apps and CO2 monitors and poo poo. not through "basic loving common sense"

my hermetically-sealed bedroom got very stuffy

thank god for my carbon dioxide sensor and phone app or I'd never have known

lol jesus christ did you spend $300 to tell you that you need airflow in your bedroom

quote source: future administrator, now former administrator

# ? Oct 29, 2023 00:02

Steve Yun: Aug 7, 2003; I'm a parasitic landlord that needs to get a job instead of stealing worker's money. Make sure to remind me when I post.; Soiled Meat

Skinnymansbeerbelly posted:

I don't know if I'm maybe just thread poisoned or what but I think the director of When Evil Lurks has some opinions about COVID & society.

oooOOOOooh

google a review, it seems others have noticed this too

# ? Oct 29, 2023 00:02

sonatinas: Apr 15, 2003; Seattle Karate Vs. L.A. Karate

icantfindaname posted:

Jesus, what country is this?

USA but then another person came
after and told me that they can do a PCR and if insurance doesn�t cover it then it�s around $100

I�m rolling the dice here lol

# ? Oct 29, 2023 00:09

Steve Yun: Aug 7, 2003; I'm a parasitic landlord that needs to get a job instead of stealing worker's money. Make sure to remind me when I post.; Soiled Meat

I�ve had corsi cubes running in the bedrooms and Living Room, but I realize now that attic airspace might be shared between my unit and the nextdoor units, so maybe I will get more cubes

Maybe add some weatherstripping to the attic entrance

# ? Oct 29, 2023 00:13

Platystemon: Feb 13, 2012; BREADS

Steve Yun posted:

I�ve had corsi cubes running in the bedrooms and Living Room, but I realize now that attic airspace might be shared between my unit and the nextdoor units, so maybe I will get more cubes

Maybe add some weatherstripping to the attic entrance

Invite skunks to live in your attic so that you will have a heads‐up if there�s air infiltration.

# ? Oct 29, 2023 00:15

Skinnymansbeerbelly: Apr 1, 2010

If you haven't gone full soda lime are you even trying?

# ? Oct 29, 2023 00:18

Zantie: Mar 30, 2003; Death. The capricious dance of Now You Stop Moving Forever.

https://twitter.com/SolidEvidence/status/1718396890708857028

JN.1 chimera in NY?

:hmmrona:

# ? Oct 29, 2023 00:27

Shady Amish Terror: Oct 11, 2007; I'm not Amish by choice. 8(

Realized it's probably not a good idea to go into too much detail on this site, but I'm very worried for my family now because one admitted to a health event their doctor attributes to covid, but they're still not masking and they're not worried about the paxlovid price hike because they are up to date on boosters and plan to keep doing so, because 'that should protect us from %90 of it'. Like, gently caress's sake, if that's the case, then that last 10% already almost killed you once, and you clearly think reinfection is possible if you're keeping up on boosters, so ????

I kind of resent the murder of public health as a concept.

# ? Oct 29, 2023 00:28

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# ? May 23, 2024 03:23

Pingui: Jun 4, 2006; WTF?

Zantie posted:

(..)
JN.1 chimera in NY?

It increases the mutational space a bit, but seeing what BA.2.86* can cook up on its own, seems more likely to get jumps in immune evasion (to me, a layman) :shrug:

# ? Oct 29, 2023 00:49

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

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