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Daniel Hurdiss @danielhurdiss.bsky.social · 21/09/2026

Excited to share that our norovirus NS3 study is now online in Nature Communications! 🎉 These enzymes, found across an entire order of RNA viruses, have long been molecular motors in search of a function. We think we’ve uncovered their role. (🧵) www.nature.com/articles/s41... #virology #cryoEM

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Daniel Hurdiss @danielhurdiss.bsky.social · 09/09/2026

Our first #cryoEM map from the Krios 5 recently installed at Utrecht University as part of the EMPower-funded upgrades to NeCEN. Hopefully the first of many more!

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Daniel Hurdiss @danielhurdiss.bsky.social · 04/09/2026

New studiewijzer just dropped. Operation Learn Dutch or Die Trying: B2.1 edition 🇳🇱🫡

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

Finally, MD simulations suggested that GT3, but not the shorter GD3 ganglioside, presents its glycan chain in a geometry compatible with spike binding at the cell membrane. They also indicate that the spike may need to approach at an angle and rearrange nearby N-glycans.

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

To connect this to airway biology, we used human nasal epithelial cultures. HKU1 infection and spike binding were restricted to ciliated cells and depended on 9-O-acetylated sialic acids. The spike signal overlapped with A2B5-reactive, GT3-like glycotopes, linking receptor display to cell tropism.

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

We then zoomed in on the binding site. The structure showed that HKU1-B engages both sialic acid residues, while mutagenesis confirmed that contacts with the second residue strengthen binding. Nearby N-glycans also tune both binding strength and linkage selectivity.

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

Next, we then determined HKU1-B spike structures with and without its preferred glycan ligand. In both cases, the spike remained fully closed, in contrast to Wang et al., who reported spontaneous, glycan-independent opening. We discuss several possible reasons for this difference in the paper.

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

First, we showed that both HKU1-A and HKU1-B spikes strongly prefer 9-O-acetylated α2,8-linked disialosides. HKU1-B bound somewhat more strongly and was also more selective, with monomeric S1A affinities of around 100 µM.

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Daniel Hurdiss @danielhurdiss.bsky.social · 06/08/2026

Why does human coronavirus HKU1 target ciliated airway cells, and do its two serotypes activate their spikes in the same way? Building on our 2023 work, we combined #cryoEM, BLI, molecular dynamics and human nasal epithelial cultures to compare serotypes A and B 🧵 www.biorxiv.org/content/10.6...

Scientific image showing how human coronavirus HKU1 may attach to cells in the nose. On the left, a microscope image shows the virus-binding part of the spike protein attaching to the hair-like surface of ciliated airway cells. On the right, a computer model shows the spike protein leaning toward the cell membrane to reach a sugar-containing molecule called GT3. This supports a possible link between sugar recognition and the virus’s preference for ciliated airway cells.

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Daniel Hurdiss @danielhurdiss.bsky.social · 20/07/2026

Really looking forward to visiting ISTA in just over two months for the 9th Austrian #CryoEM Symposium! Excited to give an EMBO YIP Lecture, hear from a great line-up of speakers, and catch up with the cryo-EM community. Hope to see you there! www.imp.ac.at/research/cry...

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Daniel Hurdiss @danielhurdiss.bsky.social · 13/07/2026

The first hetero refinement is usually quite rough, with only a relatively small fraction entering the target class, as in our recent NS3 paper. www.biorxiv.org/content/10.1...

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Daniel Hurdiss @danielhurdiss.bsky.social · 12/07/2026

Reprocessed an old Glacios dataset and pushed this Fab fragment to 3.8 Å resolution! Not a record-breaker by today’s standards, but still pretty satisfying for a C1 particle with only ~48 kDa of ordered mass. #cryoEM

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Daniel Hurdiss @danielhurdiss.bsky.social · 29/06/2026

Just back from #NIDO2026 in Hong Kong! 🇭🇰 It was a pleasure to present our latest work, catch up with colleagues, and see three Utrecht Virology Lab PhD candidates present their work. Thanks to the organisers for a fantastic meeting and EMBO YIP for the financial support. See you in Banff in 2029!

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Daniel Hurdiss @danielhurdiss.bsky.social · 29/05/2026

Honoured to receive the first Sir Dave Stuart Early Career Award today. Dave was my PhD external examiner, making this award, recognising his contributions to structural biology, especially meaningful to me. Thank you to Instruct-ERIC and Thermo Fisher Scientific for championing ECRs.

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Daniel Hurdiss @danielhurdiss.bsky.social · 02/03/2026

Excited to welcome @tejashyamk.bsky.social to the ERC starting grant team, as he starts his PhD! Teja joins us from @sc-lab.bsky.social, where he built a solid foundation in biochemistry & #cryoEM 🔬 He’ll be uncovering new insights into norovirus replication and assembly. Exciting science ahead!

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Daniel Hurdiss @danielhurdiss.bsky.social · 17/01/2026

Back from the Physics of Viruses and Protein Cages GRC in the beautiful Tuscan hills. Great to see the latest developments in the field and to catch up with familiar faces. Thanks to the organisers for the invitation to present, and to everyone I spoke with for the excellent discussions.

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Daniel Hurdiss @danielhurdiss.bsky.social · 04/12/2025

My favourite experiment in the whole study is the negative-stain polyclonal epitope mapping we did using elephant serum, affectionately known in the lab as Ellie-EMPEM 😄

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Daniel Hurdiss @danielhurdiss.bsky.social · 04/12/2025

How can AI and #cryoEM help save some of the biggest babies on the planet? 🐘🔬 Our new preprint identifies Elephant Herpesvirus gH/gL/gO as a receptor-binding complex and a promising vaccine candidate, now being tested in young elephants across European zoos! 💉 www.biorxiv.org/content/10.6...

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Daniel Hurdiss @danielhurdiss.bsky.social · 02/12/2025

Honoured to be selected as one of this year’s EMBO Young Investigators! Grateful to my team and colleagues for all their support, and excited about the opportunities this will create for my group and for our work in structural virology. www.embo.org/press-releas...

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Daniel Hurdiss @danielhurdiss.bsky.social · 14/11/2025

Had a great time hosting @proteincapsid.bsky.social over the past few days. Thanks for the exciting lecture and for sharing your tomography expertise. Until next time!

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Daniel Hurdiss @danielhurdiss.bsky.social · 26/09/2025

Rounding off an incredibly busy week with the excellent third installment of the Dutch Structural Biology Meeting! Many thanks to Arjen for the kind invitation to present our lab’s work.

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Daniel Hurdiss @danielhurdiss.bsky.social · 13/09/2025

Back from the 9th International Calicivirus Conference in Banff! Robin Veenstra and I really enjoyed both the stunning mountain views and the exciting science being shared in the field. Thanks to the organisers for putting together this great meeting. Lots of exciting collaborations ahead!

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Our model could help reconcile noroviruses, and perhaps enteroviruses, with other positive-strand RNA viruses that use large “crown” complexes to couple genome replication with RNA export. NS3 may represent a minimalist alternative to this strategy.

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Putting all of this together, we propose that NS3 transports newly synthesised plus-strand RNA from within single-membrane vesicles. Once exported, the RNA can be translated or packaged in the cytoplasm. A streamlined mechanism for linking replication to the next steps.

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Similar predictions of NS3 and its enterovirus homolog 2C, including a 50-mer polyA strand, suggest a plausible path for RNA translocation. This may point to a conserved mechanism among SF3 ATPases in positive-strand RNA viruses (but further validation is needed)!

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Here is the NTD prediction in all its glory! A compact, high-confidence transmembrane channel with convincing architecture and hydrophobicity profile. The pore is positively charged, suggesting it could help guide negatively charged RNA through the membrane. Looks solid to us!

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Amazingly, this gave us a high-confidence transmembrane channel for both mouse and human NS3, with oleic acids forming a bilayer-like pattern. Our group now call this the “fatty acid hack.” The #alphafold predictions with and without fatty acids shown below 👇

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

At this point, the missing piece of the puzzle was the N-terminal membrane-binding domain, which we had replaced with a soluble hexamerization domain to enable structural studies 🧩 To understand the full picture, we turned to #AlphaFold3.

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Does our hex-NS3 construct bind RNA? 🧬 Yes! Single-molecule magnetic tweezers experiments with the @dulinlab.bsky.social show binding to ssRNA and dsRNA, with compaction of the latter. No ATP-driven helicase activity detected (thoughts on that in the paper).

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

The nucleotide-binding sites were particularly well resolved. Clear density for ATPγS, Mg²⁺, coordinating residues, and water molecules! 🤩 A great starting point for structure-based drug design! 💊

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

The NS3 hexamer adopts a split lock-washer conformation, characteristic of AAA+ ATPases that use a hand-over-hand translocation mechanism. Also, it kind of looks like a Rolo...

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

From ~1000 images collected on a Glacios (thank you @ievadr.bsky.social!), we obtained a 2.9 Å resolution #cryoEM map of NS3 in complex with ATPγS. This gave us our first high-res look at the norovirus NS3 hexamer in action! It is a fun (and small) data set. We have uploaded this to EMPIAR.

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Their N-terminal membrane-binding region, essential for proper assembly, has also made them difficult to study in an oligomeric form. To overcome this, we engineered a soluble, hexameric version of norovirus NS3. Big thanks to @joostsnijder.bsky.social lab for mass spec/photometry work!

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

For DNA viruses, pioneering studies have shown how SF3 proteins work as replicative helicases. They unwind DNA using coordinated, ATP-driven conformational changes across a hexameric ring. But no equivalent structures are available for SF3 proteins encoded by RNA viruses...

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Daniel Hurdiss @danielhurdiss.bsky.social · 18/06/2025

Latest preprint from the lab, many years in the making! By combining #cryoEM with #AlphaFold3 modelling, we propose that norovirus NS3 forms a transmembrane RNA translocase. This could have big implications for our understanding of viral replication & assembly (🧵) www.biorxiv.org/content/10.1...

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Daniel Hurdiss @danielhurdiss.bsky.social · 23/05/2025

Think coronavirus spikes have run out of surprises? Think again. Our latest preprint dives into the highly unusual spikes of marine mammal coronaviruses. www.biorxiv.org/content/10.1... This #cryoEM study was led by @viralfusion.bsky.social, with key contributions from an amazing team.

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Daniel Hurdiss @danielhurdiss.bsky.social · 21/05/2025

Very proud of Judith Ahr who gave her final MSc internship presentation this week! Judith led an AI-driven antiviral biologics project with incredible independence. In addition, she supported many others in the lab with her expertise. We’ll miss you and can’t wait to see what’s next!

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Daniel Hurdiss @danielhurdiss.bsky.social · 19/05/2025

Height and youth proved too much for me on this occasion, but we all put in strong sub-50 minute times! 😃

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Daniel Hurdiss @danielhurdiss.bsky.social · 26/03/2025

I’m delighted that we could contribute the #cryoEM data to this incredible antiviral discovery project from the group of @neytsjohan.bsky.social 💊 "A coronavirus assembly inhibitor that targets the viral membrane protein" www.nature.com/articles/s41... A huge congrats to everyone involved! 🎉

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Daniel Hurdiss @danielhurdiss.bsky.social · 13/03/2025

Our third GPU workstation is up and running! Excited to see what this can churn out in the next few years 🚀

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Daniel Hurdiss @danielhurdiss.bsky.social · 12/02/2025

Might just be the best package I've ever received from a collaborator. God bless the Belgians! 🇧🇪🍻

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Daniel Hurdiss @danielhurdiss.bsky.social · 17/01/2025

There's nothing quite like the excitement of seeing 2D classes of a protein for the first time—but witnessing the first CPE of a virus your lab is just starting to work on is equally satisfying! 🦠

Cells displaying cytopathic effect due to virus infection.

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Daniel Hurdiss @danielhurdiss.bsky.social · 02/12/2024

Had a great day at the 10th anniversary Science for Life meeting. My personal highlights were the incredible #cryoET talk from Julia Mahamid, and @bobcoelingh.bsky.social winning a poster prize! 🏆

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Daniel Hurdiss @danielhurdiss.bsky.social · 30/11/2024

Greatly enjoying our ongoing #cryoET adventures. My new favourite way to procrastinate from administrative tasks is to play I spy with @bobcoelingh.bsky.social's recent data set! 👀 Here's an easy one! 👇

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Daniel Hurdiss @danielhurdiss.bsky.social · 16/11/2024

In some cases, 3D classification w/o alignments alone might be sufficient. Example below from one of our recent papers: doi.org/10.1073/pnas...

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Daniel Hurdiss @danielhurdiss.bsky.social · 16/11/2024

Typical pipeline looks like this nice example from the @veeslerlab.bsky.social 10.1016/j.cell.2022.05.019

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Daniel Hurdiss @danielhurdiss.bsky.social · 15/11/2024

Sharing recent publications just for fun (part 1). Here, we explored neutralizing epitopes in the porcine deltacoronavirus spike glycoprotein. 🐖 📄 www.nature.com/articles/s41... We found that a mAb targeting the N-terminus can trigger partial opening, perhaps mimicking a co-receptor interaction.

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Daniel Hurdiss @danielhurdiss.bsky.social · 12/11/2024

Incredible #virology talks today from Manon Laporte and Johan Neyts at #PRPconference2024. I'm glad we could contribute #cryoEM data to one of these exciting antiviral discovery projects! 💊 p.s. I seem to have influenced Johan to join bluesky, so please give him a follow 😉 @neytsjohan.bsky.social

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