Ryan Hisner
@ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.
...like CovSpectrum & @kgandersen.bsky.social's Outbreak, has been senselessly denied access to essential SARS-CoV-2 genomic data by the pathological liar, con man, & non-scientist who tyrannically runs GISAID. This is a travesty and a stain on science and shouldn't be tolerated any longer.
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November 13, 2025 at 12:23 AM
...like CovSpectrum & @kgandersen.bsky.social's Outbreak, has been senselessly denied access to essential SARS-CoV-2 genomic data by the pathological liar, con man, & non-scientist who tyrannically runs GISAID. This is a travesty and a stain on science and shouldn't be tolerated any longer.
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BA.3.2.2 nearly 50% of recent Western Australia sequences—perhaps on a path to dominance there?
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
November 13, 2025 at 12:23 AM
BA.3.2.2 nearly 50% of recent Western Australia sequences—perhaps on a path to dominance there?
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
Bossman. Perfect companion piece to the Big Bossman action figure. Such a close resemblance too.
November 12, 2025 at 2:57 AM
Bossman. Perfect companion piece to the Big Bossman action figure. Such a close resemblance too.
BA.3.2 has arrived in the UK. One BA.3.2.2, collected October 5, was uploaded from Scotland today.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
November 7, 2025 at 12:10 PM
BA.3.2 has arrived in the UK. One BA.3.2.2, collected October 5, was uploaded from Scotland today.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
I don't know how to square the absence of rhinoviruses (RV) in early fall here with the remarkably consistent, massive surge in RV that Biofire registers precisely when the school year starts every year. It's always the biggest peak of the year for them.
Is it a strain that doesn't register in WW?
Is it a strain that doesn't register in WW?
November 2, 2025 at 7:33 PM
I don't know how to square the absence of rhinoviruses (RV) in early fall here with the remarkably consistent, massive surge in RV that Biofire registers precisely when the school year starts every year. It's always the biggest peak of the year for them.
Is it a strain that doesn't register in WW?
Is it a strain that doesn't register in WW?
First-world problem, I know, but I can't stand it when supplementary information is contained in 20 different files that have to be individually downloaded and viewed. Why not put it all in one PDF?
October 25, 2025 at 3:16 PM
First-world problem, I know, but I can't stand it when supplementary information is contained in 20 different files that have to be individually downloaded and viewed. Why not put it all in one PDF?
In this case & others, it's difficult to know for sure whether this person received molnupiravir treatment recently or many months ago. KP.3.1.1 last circulated in Australia 10+ months ago, so this person has been infected a long time.
More sequence details pictured below. 3/4
More sequence details pictured below. 3/4
October 25, 2025 at 2:43 PM
In this case & others, it's difficult to know for sure whether this person received molnupiravir treatment recently or many months ago. KP.3.1.1 last circulated in Australia 10+ months ago, so this person has been infected a long time.
More sequence details pictured below. 3/4
More sequence details pictured below. 3/4
Positive selection means that these mutations are adaptive & are improving intrahost viral fitness.
Closer examination further strengthens the case, as per usual. G->A mutations are the most distinctive marker of MOV, & this is exactly where the bulk of the positive selection takes place. 2/4
Closer examination further strengthens the case, as per usual. G->A mutations are the most distinctive marker of MOV, & this is exactly where the bulk of the positive selection takes place. 2/4
October 25, 2025 at 2:43 PM
Positive selection means that these mutations are adaptive & are improving intrahost viral fitness.
Closer examination further strengthens the case, as per usual. G->A mutations are the most distinctive marker of MOV, & this is exactly where the bulk of the positive selection takes place. 2/4
Closer examination further strengthens the case, as per usual. G->A mutations are the most distinctive marker of MOV, & this is exactly where the bulk of the positive selection takes place. 2/4
I can't reply to this comment, so I guess I'll quote-reply.
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
October 25, 2025 at 2:43 PM
I can't reply to this comment, so I guess I'll quote-reply.
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
ORF1a:V1320L is in a prominent T-cell epitope, but it's an extremely rare mutation, especially in recent years. Only 37 sequences have had it the past 3.5 years—since April 1, 2022.
October 23, 2025 at 4:59 PM
ORF1a:V1320L is in a prominent T-cell epitope, but it's an extremely rare mutation, especially in recent years. Only 37 sequences have had it the past 3.5 years—since April 1, 2022.
The regions around the FCS have also been completely reconfigured in BA.3.2. On top of Omicron's H655Y (which increases the time spent in intermediate fusion configurations), it has K529N, E554D, A575S, E583D, H625R, N641K, V642G, and E654K upstream and A688D + S704L downstream of the FCS. 9/12
October 22, 2025 at 1:28 PM
The regions around the FCS have also been completely reconfigured in BA.3.2. On top of Omicron's H655Y (which increases the time spent in intermediate fusion configurations), it has K529N, E554D, A575S, E583D, H625R, N641K, V642G, and E654K upstream and A688D + S704L downstream of the FCS. 9/12
Also, while the FCS lab experiments are immensely valuable, they took place on an ancestral spike background. BA.3.2 not only has (relative to WT) N679R and P681H. P61H has been shown many times over to increase spike cleavage, and N679R likely has a similar effect. 7/12
October 22, 2025 at 1:28 PM
Also, while the FCS lab experiments are immensely valuable, they took place on an ancestral spike background. BA.3.2 not only has (relative to WT) N679R and P681H. P61H has been shown many times over to increase spike cleavage, and N679R likely has a similar effect. 7/12
Importantly, there has never been a variant with a deletion like this. Though there were a very small number of early reports of FCS deletions, I'm skeptical they were real. All were from the same lab, led by a fraudulent scientist (Didier Raoult) who's since had 48 papers retracted. 6/12
October 22, 2025 at 1:28 PM
Importantly, there has never been a variant with a deletion like this. Though there were a very small number of early reports of FCS deletions, I'm skeptical they were real. All were from the same lab, led by a fraudulent scientist (Didier Raoult) who's since had 48 papers retracted. 6/12
What's certain is that the ∆QTQTN deletion reduces (furin) S1/S2 cleavage. The smaller ∆QT in this BA.3.2 (assuming it is real, as it appears to be), likely has a similar tendency. 5/12
October 22, 2025 at 1:28 PM
What's certain is that the ∆QTQTN deletion reduces (furin) S1/S2 cleavage. The smaller ∆QT in this BA.3.2 (assuming it is real, as it appears to be), likely has a similar tendency. 5/12
Oddly, despite reduced illness and demonstrably reduced cell entry in vitro, viral replication was apparently increased in hamsters in the nose and throat (as measured by viral RNA titers), while lung replication was unchanged.
Hard to make sense of. 4/12
Hard to make sense of. 4/12
October 22, 2025 at 1:28 PM
Oddly, despite reduced illness and demonstrably reduced cell entry in vitro, viral replication was apparently increased in hamsters in the nose and throat (as measured by viral RNA titers), while lung replication was unchanged.
Hard to make sense of. 4/12
Hard to make sense of. 4/12
But in human lung cancer (Calu3) cells, the ∆QTQTN-mutant replication was dramatically reduced (2.5 orders of magnitude), and in infected hamsters disease was much milder. 3/12
October 22, 2025 at 1:28 PM
But in human lung cancer (Calu3) cells, the ∆QTQTN-mutant replication was dramatically reduced (2.5 orders of magnitude), and in infected hamsters disease was much milder. 3/12
Work by @themenacherylab.bsky.social was looked at a similar, but more extensive, deletion. They deleted both QT repeats plus the next AA (∆QTQTN). In Vero cells (monkey kidney cells), it produced extra-large plaques & outcompeted WT virus—similar to furin cleavage site (FCS)-deletion mutants. 2/12
October 22, 2025 at 1:28 PM
Work by @themenacherylab.bsky.social was looked at a similar, but more extensive, deletion. They deleted both QT repeats plus the next AA (∆QTQTN). In Vero cells (monkey kidney cells), it produced extra-large plaques & outcompeted WT virus—similar to furin cleavage site (FCS)-deletion mutants. 2/12
I beg to differ! If it's not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
October 22, 2025 at 11:46 AM
I beg to differ! If it's not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
I can see I'm going to get a lot of mileage out of this Thoreau quote in the near future.
October 21, 2025 at 4:28 PM
I can see I'm going to get a lot of mileage out of this Thoreau quote in the near future.
My only slight quibble: absence of one of the essential N-terminal spike glycans (gained through either T22N or ∆S31), which have been ~universal for well over a year now. Still, this is great work by @veeslerlab.bsky.social.
October 21, 2025 at 12:12 PM
My only slight quibble: absence of one of the essential N-terminal spike glycans (gained through either T22N or ∆S31), which have been ~universal for well over a year now. Still, this is great work by @veeslerlab.bsky.social.
Due to antigenic imprinting (also called "original antigenic sin", or OAS) the antibody response is slow to turn, but turn it will, with enough repeated, UPDATED vaccinations.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Or repeated infections, I suppose, if you prefer suffering and poor health.
October 21, 2025 at 12:12 PM
Due to antigenic imprinting (also called "original antigenic sin", or OAS) the antibody response is slow to turn, but turn it will, with enough repeated, UPDATED vaccinations.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Adam Smith,W. of Nations
"The man whose whole life is spent in performing a few simple operations… has no occasion to exert his understanding... He naturally loses, therefore, the habit of such exertion, and generally becomes as stupid and ignorant as it is possible for a human creature to become."
"The man whose whole life is spent in performing a few simple operations… has no occasion to exert his understanding... He naturally loses, therefore, the habit of such exertion, and generally becomes as stupid and ignorant as it is possible for a human creature to become."
October 21, 2025 at 11:38 AM
Adam Smith,W. of Nations
"The man whose whole life is spent in performing a few simple operations… has no occasion to exert his understanding... He naturally loses, therefore, the habit of such exertion, and generally becomes as stupid and ignorant as it is possible for a human creature to become."
"The man whose whole life is spent in performing a few simple operations… has no occasion to exert his understanding... He naturally loses, therefore, the habit of such exertion, and generally becomes as stupid and ignorant as it is possible for a human creature to become."
Thoreau, FTW, forever.
"Where is this division of labor to end? and what object does it finally serve? No doubt another may also think for me; but it is not therefore desirable that he should do so to the exclusion of my thinking for myself." —Henry David Thoreau
"Where is this division of labor to end? and what object does it finally serve? No doubt another may also think for me; but it is not therefore desirable that he should do so to the exclusion of my thinking for myself." —Henry David Thoreau
October 21, 2025 at 11:38 AM
Thoreau, FTW, forever.
"Where is this division of labor to end? and what object does it finally serve? No doubt another may also think for me; but it is not therefore desirable that he should do so to the exclusion of my thinking for myself." —Henry David Thoreau
"Where is this division of labor to end? and what object does it finally serve? No doubt another may also think for me; but it is not therefore desirable that he should do so to the exclusion of my thinking for myself." —Henry David Thoreau
Reminiscent of Thorstein Veblen's work. Jobs with "no taint of usefulness" are the most respectable—and the most highly paid—while manual labor or anything smacking of usefulness "is of course on a precarious footing as regards respectability"—and, it goes without saying, are poorly paid.
October 20, 2025 at 11:29 AM
Reminiscent of Thorstein Veblen's work. Jobs with "no taint of usefulness" are the most respectable—and the most highly paid—while manual labor or anything smacking of usefulness "is of course on a precarious footing as regards respectability"—and, it goes without saying, are poorly paid.
I realized later today that I'd given the S:T124I mutation in this new sequence short shrift.
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
October 13, 2025 at 9:04 PM
I realized later today that I'd given the S:T124I mutation in this new sequence short shrift.
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3