Jason Yeung
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jayeung12.bsky.social
Jason Yeung
@jayeung12.bsky.social
330 followers 500 following 30 posts
MD-PhD candidate @utmbhealth interested in viruses and data science | Former ballet dancer using publicly available dance data for advocacy
https://jason-yeung.netlify.app/
https://datapointesguide.com/
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jayeung12.bsky.social
What is going on with ldlr proteins and arboviruses?? Some kind of vector/mammalian host coevolutionary constraint??
October 29, 2025 at 7:48 PM
jayeung12.bsky.social
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:
Text reading - Broader principle of multimeric polymerase structures dictating possible recombination mechanisms - 'Engineering' demands for greater control over transcription - [[@Viral Genome Principles]] - [[@Segmentation in viruses may allow for more precise gene regulation]] - [[Evolution and Emergence of RNA Viruses]] by [[Edward C. Holmes]] - [[Genome Modularity]] - Demarcation by or acquisition of TRS allows for viral reassortment or new gene formation in a relatively modularized fashion - High fidelity of replication needed to be evolutionarily acquired first before expansion of the genome/elaboration of the TRS subgenomic recombination gene regulation system(?) - How does this work in that bisegmented coronavirus? - [[@Identification and genomic characterization of a novel bisegmented coronavirus in the lesser panda]] - Categorizing everything as the copy choice model is imprecise as there can be many distinct routes to this outcome - [[Viral Recombination Mechanisms]] - Polymerase processivity, fidelity, and speed all relate to backtracking probability - [[Polymerase Backtracking]], [[RdRp Backtracking]] Text reading - What is the trigger for TRS sequences? Backtracking related? - Maybe - No direct demonstration that they are related that I've noted - Most definitely secondary structure dependent in my mind - arteriviruses and coronaviruses both employ TRS - Many different TRS sequences, so not strictly sequence dependent - Engineerability with non-natural TRS in recombination-deficient viruses - Doesn't even need to be a linear piece of nucleic acid, can be circular with TRS and still work - [[@Discontinuous template switching generates coronavirus subgenomic RNAs from the 3ʹ viral genome end by 5ʹ to 3ʹ transcription]] - [[@An atomistic model of the coronavirus replication-transcription complex as a hexamer assembled around nsp15]] - > Finally, the original template would need to unwind from the nascent strand for polymerization to continue on the new template. As with proofreading, we propose the shift in the dsRNA position upon base pairing of the nascent strand to the TRS-L triggers activation of nsp13 and backtracking of the template. This would unwind the original template from the nascent strand, while leaving it base paired with the new template (Fig. 7E). Once unwinding is complete, the dsRNA formed at the TRS-L juncture with the new template could shift back into the polymerase active site and finish synthesis on the remaining nucleotides of the 5′ leader (Fig. 7F) - > We should note that binding of the N protein to the nsp13 dimer appears to block access to the nsp13.1 RNA-binding groove, suggesting that nsp13.2 may govern backtracking in this situation. While the template has so far been seen by cryo-EM only engaging with nsp13.1, modeling of the relevant states indicates that nsp13.2 could perform this backtracking function as well. Thus, it may be that nsp13.1 governs backtracking for proofreading during positive-strand synthesis, but nsp13.2 governs backtracking for proofreading and transcription during negative-strand s… Text reading - nucleoside/nucleotide analogs influence backtracking probability because they are incorporated on the growing strand, what about nucleic acid modifications on the template strand? - I think it's unlikely but recombination probabilities could be correlated with modification maps across coronavirus genomes - m6a or 5mc not a sequence dependent minimal trigger for programmed backtracking - can still replicate virus in KO cell lines for writer proteins so presumably does not eliminate sgmRNA production - Other proteins besides core RTC complex involved? - Exo and endonucleases - [[@Commentary on Routh Menachery nsp15 paper]] - [[@SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness]] - [[Coronavirus nsp14]] - [[@The coronavirus proofreading exoribonuclease mediates extensive viral recombination]] collapsed:: true - > significant preference for a UUG motif - > MHV-ExoN(-) mutants showed decreased recombination junction frequency and altered populations of sgmRNAs and DVGs - > whether nsp14 ExoN alleviates backtracking as proposed - quote from [[@Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir]] - This prediction does not align with what was observed in [[@The coronavirus proofreading exoribonuclease mediates extensive viral recombination]] collapsed:: true - If ExoN increases recombination, shouldn't it promote backtracking in certain contexts if that is what mediates all non-homologous recombination (including sgmRNA formation)? - Sequence specificity and preference for recombination at poly U tracts perhaps due to polymerase slipping and subsequent backtracking - A bit surprised to see copyback events [[Copy-Back RNAs]] detected given no(?) reports of these being generated based on sequencing data - [[@Defective viral genome detection review]] -
October 8, 2025 at 3:55 PM
jayeung12.bsky.social
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
labwaggoner.bsky.social Waggoner Lab @labwaggoner.bsky.social · Apr 2
Unique B Cell and Germinal Center Responses in Mice with Severe versus Mild Orientia tsutsugamushi Infection
www.biorxiv.org/content/10.1...
April 2, 2025 at 2:49 AM
jayeung12.bsky.social
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…
ywangapril.bsky.social ywangapril.bsky.social @ywangapril.bsky.social · Mar 28
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!
Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688 | PNAS
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent p...
www.pnas.org
March 29, 2025 at 2:12 AM
Reposted by Jason Yeung
ywangapril.bsky.social
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!
Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688 | PNAS
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent p...
www.pnas.org
March 28, 2025 at 7:49 PM
Reposted by Jason Yeung
biorxiv-microbiol.bsky.social
The furin cleavage site is required for pathogenesis, but not transmission of SARS-CoV-2 https://www.biorxiv.org/content/10.1101/2025.03.10.642264v1
March 12, 2025 at 1:42 AM
Reposted by Jason Yeung
yawshinooi.bsky.social
Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses

www.pnas.org/doi/10.1073/...
PNAS
Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
www.pnas.org
February 19, 2025 at 5:46 PM
jayeung12.bsky.social
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.
February 11, 2025 at 5:48 AM
jayeung12.bsky.social
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)
biorxiv-microbiol.bsky.social bioRxiv Microbiology @biorxiv-microbiol.bsky.social · Feb 7
DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication https://www.biorxiv.org/content/10.1101/2025.02.04.636569v1
February 8, 2025 at 4:33 AM
Reposted by Jason Yeung
profmarciniak.bsky.social
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?
January 18, 2025 at 8:27 AM
jayeung12.bsky.social
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. ->
index
datapointesguide.com
January 9, 2025 at 3:58 PM
Reposted by Jason Yeung
taha801.bsky.social
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 🧵
January 3, 2025 at 7:55 PM
Reposted by Jason Yeung
idsainfo.bsky.social
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.
A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms
In early April 2024 we studied two Texas dairy farms which had suffered incursions of H5N1 highly pathogenic avian influenza virus (HPAIV) the previous month.
academic.oup.com
December 24, 2024 at 7:33 PM
Reposted by Jason Yeung
lenasteckelberg.bsky.social
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
December 20, 2024 at 1:27 PM
jayeung12.bsky.social
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...
Mechanistic Insights into Dengue Virus Inhibition by a Clinical Trial Compound NITD-688
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent pan-serotype DENV inhibitor currently in Phase II clin...
www.biorxiv.org
December 16, 2024 at 7:33 PM
Reposted by Jason Yeung
polybiorf.bsky.social
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.”
December 12, 2024 at 4:05 PM
jayeung12.bsky.social
Doing adventofcode.com to build up those Rust skills! 🎄🦀 Joined late but it's resolving my "I have no reason to use Rust" dilemma
Advent of Code 2024
adventofcode.com
December 6, 2024 at 4:08 AM
Reposted by Jason Yeung
mjpallen.bsky.social
Letter sent in to the Editor of the Guardian on brain microbiome nonsense.
December 3, 2024 at 10:01 AM
Reposted by Jason Yeung
harschnitz.bsky.social
Our study describing inherited DBR1 deficiency leading to SARS-CoV-2 brainstem encephalitis in @jexpmed.bsky.social made the cover! DBR1-mutated hindbrain neurons are susceptible to SARS-CoV-2. Great collaboration with the Rice, Studer, Casanova, Ekwall & Zhang teams.

doi.org/10.1084/jem....
September 12, 2024 at 5:13 AM
jayeung12.bsky.social
What a paper. I somehow missed all of the UTMB seminars about this work. There sorely needs to be an updated review article on the molecular basis for coronavirus recombination because I keep getting lost in the weeds. Some thoughts:
A picture of text organized in a list. The text reads: - *__Recombination at poly-U regions still occurred with catalytic inactivation of nsp15__* and *__delDVGs increased while sgmRNA decreased__*. Three potential ways nsp15 catalytic mutants increase non-homologous recombination (not mutually exclusive): - Perhaps this is tied to switch between genome replication and transcription? - > "It is conceivable that the endoU activity of NSP15 may play a role in mediating the template switching between +gRNA and -sgmRNA to give rise to +sgmRNA." - If delDVGs are only generated during genome replication, the increase in delDVGs could be due to a deficit in switching to sgmRNA-production mode. - The lower overall replication for the nsp15 mutant is likely tied to increased immune activation limiting the number of infected cells but the amount of genomic RNA per infected cell could be higher and sgRNA lower. This is suggested by *in vivo* results. - nsp15 catalytic mutants lead to increased dsRNA in highly concentrated puncta - High amounts of dsRNA provide increased opportunities for successful template switches - See the other paper on nsp15 H234A: - Otter CJ, Bracci N, Parenti NA, Ye C, Asthana A, Blomqvist EK, Tan LH, Pfannenstiel JJ, Jackson N, Fehr AR, et al.: **SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling**. *Proceedings of the National Academy of Sciences* 2024, **121**:e2320194121. - These findings may tie in with the SARS-CoV-2 polymerase backtracking story that is developing for coronavirus recombination. - Poly-U tracts and induction of polymerase backtracking have been linked for other RNA polymerases. - Theoretically, anything that could cause polymerase backtracking (poly-U, TRS secondary structures, nucleotide antivirals) has some probability of producing a recombinant viral RNA. Hence why abolishing nsp15 endoU does not get rid of the poly-U enriched pattern
November 16, 2024 at 9:14 PM
Reposted by Jason Yeung
jesseerasmus.bsky.social
Here is part 2 of the list. go.bsky.app/TWLffWH
November 12, 2024 at 2:20 AM
jayeung12.bsky.social
📢 This is my public plea 📢 for more scientific medium-form content. I discuss the "riff" as my favorite format for sharing and building relationships online. Blogging as an academic has more benefits than you may think:
jason-yeung.netlify.app/posts/2024_9...
Jason Yeung - Give Me More Medium Form Content: Enter the Riff
On the benefits of blogging, how to write a riff, and why I think more academics could benefit from creating medium-form content online.
jason-yeung.netlify.app
September 25, 2024 at 1:04 PM
jayeung12.bsky.social
Excellent piece on long COVID funding that also mentions the dissolution of the AViDD network. As someone who sat in on a few of the meetings at UTMB, there were very exciting collaborations occurring due to the grant. Hard not to see the recent ReVAMPP awards as a scaled down AViDD with new people.
laurahowes.bsky.social Laura Howes @laurahowes.bsky.social · Sep 18
Rowan's latest feature for @cenmag.bsky.social looks at attempts to develop new pharmaceutical treatments for long COVID. It is, unfortunately, not a feel-good story. 🧪 #chemsky #biotech
R&D for long COVID is collapsing
Public and private funding is lacking, scrambling opportunities to develop treatments
cen.acs.org
September 19, 2024 at 3:58 AM
jayeung12.bsky.social
An R Shiny use case I found few examples of: I built a crowdsourcing app! Submission of new info, voting on data accuracy, and cookies to avoid having to create logins. Just Google Sheets and MongoDB. Now the hard part - getting people to contribute to it
Data Pointes Contract Reporting Portal [BETA]
jasonyeung.shinyapps.io
August 9, 2024 at 3:41 PM