BA.3.2 is a highly divergent Omicron descendant that has circulated globally at low level. Here we combine live virus infection in primary human airway epithelium with cryo-EM to directly compare BA.3.2 with JN.1 descendants and uncover the structural basis of its immune-evasion–fitness trade-off.
What is going on with ldlr proteins and arboviruses?? Some kind of vector/mammalian host coevolutionary constraint??
More interesting work that furthers this thread between SARS-CoV-2 recombination, the RTC complex, polymerase backtracking, and antiviral drug mechanisms of action. The biochemistry behind viral recombination is still very much open. Some personal notes on these:
Thanks!
Yeah, we thought same--that it might be something similar to what happens with Vero passaging. It's an epithelial cell organoid (low cell growth) with replication >2 months. However, there's TMPRSS2 expression and R682W is very consistently gained in our BA.5 but not WA-1 replicates 🤷
Same. I needed to build better writing habits before I got a ton of value from it
We are getting evolution of an FCS weakening mutation in a persistent infection model. Noticed anything about R682W specifically?
No, haven’t seen any. I vaguely remember a few professional level dancers posting about lingering issues years ago on Instagram but that’s the extent
As someone who previously knew little about Orientia tsutsugamushi, it was surprising to learn how many cases there are: "Within endemic regions, commonly known as the tsutsugamushi triangle, there are an estimated one million cases annually[...]". Currently working on something related
The preprint is out! Congratulations to @ywangapril.bsky.social on this investigation into leading DENV drugs. Possible in large part due to the AViDD center grants…
Happy to share our recent study on the mechanism of a clinical #DENV inhibitor, NITD-688. For someone with a background in biophysics, it's also a learning journey into #virology, #antiviral, and academia/industry collaboration. Thanks Xuping, Pei-Yong and all the collaborators at UTMB/Novartis!
The furin cleavage site is required for pathogenesis, but not transmission of SARS-CoV-2 www.biorxiv.org/content/10.1101/2025.03....
Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses
www.pnas.org/doi/10.1073/...
Unfortunately, persistent SARS-CoV-2 seems to be confined to tissues. If a good cell/animal model for SARS-CoV-2 persistence was available, parameters from models could be adapted to understand dynamics and feedback loops required for persistence. Until then, the focus is understandable.
A lot of discussion re: assay development and tissue-level sampling for persistence. To really get at how persistence is generated needs measurable longitudinal markers amenable to mathematical modeling akin to viral load for HIV. Modeling was transformational for treatment strategies there.
This gene and PLSCR1 keep showing up in host factor CRISPR screens. Still ambiguous what they exactly do but definitely act early before interferon. Interestingly, DAZAP2 KO largely shows up as a hit when the screen has an earlier end point (shorter than 4-7 days)
Will the choroid plexus be sampled alongside other CNS tissue being examined? Despite substantial evidence for potential infection, most non-LC autopsy studies skip sampling it.
I've actually been learning Rust over this past year in large part because I kept seeing you post about it on twitter lol. Your evangelizing is working
I find it remarkable how SARS-CoV-2 remains out-of-phase with the other respiratory viruses. Hasn’t settled down to being a mainly winter infection yet.
Thoughts?
People keep telling me I should monetize it but I have no idea where I want to go with this now. Ballet was 10 years ago now. As I get more into medicine and try to wrap up my PhD, I'm finding I have less and less time and I'm finding it hard to let it die.
I love the quote "You can just do things." This was the biggest shift in thinking from this. I felt like this was my first step from being a consumer to a do-er.
In roughly 3 years, I was a leader in this niche thing of ballet analytics because no one else really did it. I've met tons of people online and it's helped my science career directly. The project website popped off and receives way more traffic than any journal article I've written (so far 🙃).
Once I learned R, I decided I was going to study ballet trajectories as a side project. To be honest, it felt trivial at the time. I learned shiny, the tidyverse, and Quarto because of it.
I just kept doing it for years and people started to notice. I shared the data freely, making some friends.
After some injuries, I read the signals--moved back home, loafed around for a year, and went to college. Yet, I had this idea that I had mismanaged my short ballet career. When I was in, I didn't research companies well and generally had no real sense of what my chances of progression were.
6 years ago, I started a data science project that landed me a board position at a non-profit featured in the NY Times.
My first career was as a professional ballet dancer straight out of high school. I was good enough to stick around and keep jobs but not to advance quickly. ->
Thrilled to share our latest work identifying that #SARSCoV2 #Omicron variants harboring an L260F mutation in NSP6 have enhanced replication and pathogenesis. A not so brief thread 🧵
In CID, Ismaila Shittu, PhD, and colleagues studied two Texas dairy farms which had suffered incursions of H5N1 highly pathogenic avian influenza virus (HPAIV) the previous month.
Hi Bluesky, just in time for the holidays I am excited to share the latest pre-print from my group! We solved the 3D structure of a mysterious viral RNA that resists degradation by host nucleases. A short 🧵 &link below – please also check out the full video! #RNA #RNAbiology #RNASky #lovevirology
It's been a momentous few years for both Dengue and DENV antiviral development - particularly for the JNJ and NITD NS4B inhibitors. New preprint from my thesis lab sheds some light on the differences between the two companies' compounds (they don't work the same way): www.biorxiv.org/content/10.1...
1/ PolyBio’s Dr. Sara Cherry asserts: “Treating [the lung] with either nirmatrelvir (Paxlovid) or molnupiravir, we clear the [SARS-CoV-2] infection by 10,000-fold… while nirmatrelvir clears the infection in intestinal cultures, molnupiravir has no activity.”
