Stuart Turville

@Jjjjjjjjjjg @veeslerlab @dabiophysicist It could… need to look at what stage of the life cycle though. It’s become a little more complex since Omicrons.

@veeslerlab @dabiophysicist @StuartTurville It would be interesting anyway to see how the variants carrying the S:813N mutation behave with respect to their use of TMPRSS2. Over time, a few cases have appeared (notably quite a few HZ.1 cases), and now also some XFY.1 cases. I’m adding the recent sequence...

How are host proteases promoting coronavirus entry into cells? Find out by reading our latest manuscript led by Matt McCallum Brett Case Jack Brown @YoungjunPark11 in collaboration with @msdiamondlab 1/19

@Nucleocapsoid @SolidEvidence Marc what does the FCS look like?

@SolidEvidence Adaptation to ACE-2 isoform only seen somewhere in gut would fit too - but is there such an isoform? Or - allà @StuartTurville - ACE-2 complexed to B0AT-1 or whatever the gut solute carrier is that chaperones ACE-2 - might have different binding to RBD, but that feels a stretch?

This cryptic has been playing peek-a-boo with me for a while, but I finally got a good look at its RBD. Little Rock, AK: 5/4/26 Some kind of early Omicron. 417T-440R-445P-450R-452M-455F-456L-460K-462R-475V-477N-478K-484A-496S-498R-501Y-505H-516Q

@Nucleocapsoid @LongDesertTrain It’s primarily why JN.1s spit out their FCS is real-time, as the only way to restore virion Spike in VeroE6 cultures is to have S1/S2 uncleaved. pubmed.ncbi.nlm.nih.gov/40056806/

@Nucleocapsoid @LongDesertTrain We have observed spike stripping from the membranes of primary isolates but not through TMPRSS2. It’s an Omicron phenotype and appears in VeroE6s and other cells with and without TMPRSS2. Spike loss is ranked JN.1=XBB>Ba.2>Delta>Ancestral.

Of interest to @StuartTurville @LongDesertTrain Unclear whether phenomenon relevant in vivo, but certainly looks like it might be in cell lines used for much lab research? High TMPRSS-2 expression interfering with functional Spike incorporation was not on my bingo card! 1/2

@BioSRP @SolidEvidence @gadboit @sanewman1 @KIR_Film_Prod @emilyakopp @rowanjacobsen @DrEricDing A better understanding of its original tropism (how Ancestral virus infected cells and tissues initially) is often a good starting point. Then with that knowledge, looking in the tissue/cells of suspected animals would be the next. In that setting data on cats is of interest.

Despite what this article states NO ONE has shown that SARS-CoV-2 infects Raccoon dogs, nor that they can transmit, BOTH are essential for a candidate origin intermediate host @SolidEvidence @gadboit @StuartTurville @sanewman1 @KIR_Film_Prod @emilyakopp @rowanjacobsen @DrEricDing

We summarize our findings in an animation made in partnership with @janetiwasa detailing the process of coronavirus entry into cells 14/19

@dabiophysicist @StuartTurville Link to the paper 20/19 nature.com/articles/s4159…

@jQcWWnq98LPRw5Z Individual vs pooled donations in late 2025…. Pooled are > 15k donors at the same time.

@jQcWWnq98LPRw5Z Single donations

Repeated SARS-CoV-2 Antigenic Exposures from Prior Vaccinations and Infections Demonstrate Limits of Antibody Durability and Breadth Against Newer Variants | bioRxiv biorxiv.org/content/10.648…

@LongDesertTrain @Nucleocapsoid @danwalker9999 BA.3.2 is an example where we often scratch our heads about how and why it is competitive. In a perfect world we would be tuning skills in the lab to generate better and better assays and datasets to know why. Alas politics of the day often doesn’t support this fundamental work

@LongDesertTrain @Nucleocapsoid @danwalker9999 Jurisdictions will influence data. So will time. In late 2025 we saw those with good responses to XFG had poor responses to BA.3.2. Poor responses to XFG then had good responses. That equation might be changing now as BA.3.2 is starting to dominate…but it took a while here.

I'm keeping open mind on whether Orf7 deletion is the ONLY factor in BA.3.2's seeming predeliction for infecting children. Different immune history of kids (e.g. fewer vaccines, esp. Wuhan original IMPRINT) has always been possible contributor we should continue to keep in mind.

@Nucleocapsoid @SolidEvidence Changes at 685 do. What is the FCS sequence now? Do you see the FCS spit out or changed like people see in Veros for cryptics? Entry into enterocytes you’d expect to retain TMPRSS2 use. Could be another cellular reservoir we haven’t mapped.

@SolidEvidence You think P681Q really "kills" the FCS?

A new cryptic lineage popped up in St Louis a few weeks ago. I’ve been sampling this sewershed (500k people) twice a week for years and the first time I see this cryptic lineage it is 5 years old and makes up 50% of the sample. 1/

@ZdenekVrozina @Jjjjjjjjjjg @Nucleocapsoid Chp has high levels of Collectrin and that would consume the solute carriers that ACE2 would potentially chaperone. In that setting… lack of ACE2-solute complexes, Omicrons would be heavily attenuated….. that’s a prediction though that would need to be confirmed in vivo.

So, phenotypes such as syncytia, tropism, or barrier dysfunction are emergent properties of the interaction between SARS2 and the cellular context - not fixed intrinsic traits of the virus itself. And how this manifests in the Chp remains unclear, as it is inherently tissue specific.

I haven't posted in a while as we've been scratching our heads for the last year trying to understand a virus that spreads amongst. For us it was to understand how a virus that caused our most recent pandemic changed. It was also crucial to resolve for continued surveillance.

New article by @kakape on GISAID, data sharing, & apps being cut off. It's not about COVID - it's about *all* viral data, it's about data sharing being step 1 for preparedness, response, & treatment/vaccines. So we should ensure our DBs live up that. science.org/content/articl…

@CovidSafeNZ @Tuliodna Others have looked at this specifically with KP.2 based formulations. Eg. pubmed.ncbi.nlm.nih.gov/41288098/ Any booster will help with increasing breadth across all variants. Some a little better when matched well.

@StuartTurville @Tuliodna Does this have any implications for the efficacy of the JN.1 vaccine vs the LP.8.1 vaccine which builds a better response against XFG? The LP.8.1 vaccine is approved but not yet available here in NZ.

SARS-CoV-2 continue to surprise us with evolutionary jumps. In this pre-print, we describe the Identification and genomic characterisation of BA.3.2: a highly divergent BA.3-related SARS-CoV-2 lineage from southern Africa. A thread 🧵 medrxiv.org/content/10.648…

@Tuliodna 15. As for other tissue and transmissibility, it may need a few more changes to establish better ACE2 binding and then TMPRSS2 to get to levels like we saw with JN.1. But this lineage and many others are still with us and worth monitoring for key phenotypic changes in the future

@Tuliodna 14. The complications of lower respiratory infections observed with earlier pre-omicron variants may indeed not transpire as the requirements for replication are not favourable in that tissue. i.e. RAS-ACE2 attenuates BA.3.2.2 and other Omicrons as it reduces TMPRSS2 use.