So the following four multi-A->G mutation patterns have shown up in sequences collected July 30 or later. These are all in the spike NTD. In each case, all the mutations were acquired in one step. The bottom one has appeared in numerous US states. What's going on here? 1/3
To be clear, I have no idea. I can't recall ever seeing clusters of A->G mutations like this before. There's a human enzyme called ADAR that can causes A->G mutations. Is there something in the JN.1 secondary RNA structure in this region that attracts ADAR? 2/3
These are not the only multi-A->G mutation clusters in this area. A 2-nuc version of K150R has appeared many times, sometimes w/K147E, & two sequences seem to have acquired K150R via recombination with NSP15.
Just throwing this out there to see if anyone has ideas. 3/3
Nothing in particular stands out about their location in the WT secondary RNA structure. But it looks like an area of low-confidence structure prediction, & there have been a lot of mutations/deletions in this region of the genome. So the real structure may be entirely different.
...to the extent that there is a "true" structure anyway. I know it tends to fluctuate and switch between different structures, probably influenced by a bunch of hard-to-account-for factors in the cellular environment.
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I've tried to make sense of BA.3.2's penchant for kids by considering its unique spike: more compact, more closed, & more antibody-evasive than any other variant.
But I think another feature of BA.3.2 is responsible: its wholesale deletion of ORF7a, ORF7b, & ORF8 (∆ORF78).
2/
∆ORF78 is rare but not unheard of; it was in several late XBB variants (GW.5.1.1, FW.1.1, GE.1.2, etc) & a few branches of other variants. I've long thought these late XBB had an advantage in some population subsector, but I didn't suspect kids. 3/
I suspect that the number of people continuously infected since 2020 or 2021 is much larger than we realize. It's impossible to prove, but there are case studies where a chronically infected person gets infected by a new variant, which drives out the original virus...
2/16
...which consequently leaves no trace that the person was chronically infected before the super-infecting variant—took over.
Why then are some Cryptic WW variants resistant to being outcompeted by newer variants?
3/16
While the final outcome for BA.3.2 is uncertain, its unique characteristics—extensively remodeled spike NTD & SD1/SD2, novel S2 muts, & total deletion of ORF7a/7b/8—make it the best candidate for co-dominance we've seen, which could mark a new era in SARS-2 evolution. 1/
Very proud to be a co-author on this comprehensive preprint on the novel, growing saltation lineage BA.3.2, together with @Tuliodna, Darren Martin, Dikeledi Kekana, and lead author @graemedor. 1/9
I would normally write a summary 🧵 of the BA.3.2 mutational analysis here, but as much of my contribution parallels my previous BA.3.2 threads I'll just link to those here, w/brief descriptions of each.
BA.3.2 emerged in Nov 2024 after ~3 years of intrahost evolution with >50 new spike AA muts, but since then, it's changed very little. Could the drug molnupiravir (MOV) galvanize BA.3.2 into pursuing new evolutionary paths? A new 89-mut MOV BA.3.2 seq suggests it could. 1/11
Background on MOV: It's a mutagenic drug. Its purpose is to cause so many mutations that the virus becomes unviable & is cleared. But we've long known this often does not happen. Instead, the virus persists in highly mutated form & can be transmitted. 2/
I was an author on a paper published in @Nature that conclusively showed not only that MOV has created highly mutated, persistent viruses, but that these viruses have transmitted numerous times. See 🧵 below by lead author @theosanderson. 3/
The most valuable viral research tools—@nextstrain & CovSpectrum—are being destroyed, not only blocked from new data but now forbidden from even sharing info from the PAST. Why?
Because GISAID is run dictatorially by a con man, paranoid egomaniac, & liar named Peter Bogner. 1/
I use CovSpectrum & Nextstrain every day—& I'm not the only one. Every Covid thread I've ever posted here has relied partly on CovSpectrum & Nextstrain for information & visuals. These vital tools have now been stolen from us by a world-class grifter. 2/ thinkglobalhealth.org/article/to-fin…
For years scientists knew something was very, very wrong with GISAID, but the breakout story (from which much of this 🧵is based) came 2 years ago in @ScienceMagazine from @sciencecohen & Martin Enserik. 3/ science.org/content/articl…