Spyros Lytras
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spyroslytras.bsky.social
Spyros Lytras
@spyroslytras.bsky.social
Incoming PI at Institut Pasteur 🇫🇷

Current: Evolutionary Virologist based at the University of Tokyo 🇯🇵


💻🦠🏳️‍🌈
Guess the news is officially out! Extremely excited to announce that I will be starting my own laboratory at Institut Pasteur @pasteur.fr this coming spring!

Slight change to my office window view from Tokyo Tower🗼 to the Tour Eiffel. 🇫🇷
November 15, 2025 at 6:42 AM
The bat viruses with the closest spike or loop2 to that of nvHKU5r-CoV were also sampled in provinces with primary mink fur processing and wholesale hubs, further implicating fur farming as an important risk factor for virus spillover.
October 28, 2025 at 5:07 AM
AlphaFold3 co-structure predictions were also consistent with entry when this single mutation was introduced, revealing the likely molecular interaction that enables hACE2 compatibility.
October 28, 2025 at 5:07 AM
Using a safe, replication competent VSV system expressing the nvHKU5r-CoV spike we did passaging in mixed cells expressing both Pabr and hACE2. To our surprise, the spikes acquired a single mutation on the loop2, R548S, which enabled hACE2 usage!
October 28, 2025 at 5:07 AM
We further confirmed our pseudovirus results with luciferase reporter live virus, showing that nvHKU5r-CoV specifically replicated well in both PabrACE2 and nvACE2 expressing cells.
October 28, 2025 at 5:07 AM
Impressively, AlphaFold3 predictions of RBD-ACE2 pairs were very consistent with pseudovirus results! RBDs with ACE2 entry had consistent binding footprints while RBDs without entry were predicted to bind inaccessible parts of the ACE2s.
October 28, 2025 at 5:07 AM
...the only two long loop2 RBDs that can use nvACE2 being nvHKU5r-CoV and Q265, but not WZ2! This shows that loop2 is a key determinant for enabling the use of non-bat ACE2s.
October 28, 2025 at 5:07 AM
Taking these RBDs in the lab, we show with pseudovirus assays that all HKU5r-CoVs can use their native P abramus ACE2, but only few can use mink ACE2, especially ones with long loop2s...
October 28, 2025 at 5:07 AM
This part of the RBD corresponds to a loop in the RBD structure called loop2, known to have different lengths between HKU5r-CoVs. By examining the evolution of the loop2 we show a single deletion to a shorter genotype which has in turn recombined into many different RBDs.
October 28, 2025 at 5:07 AM
However, just like all CoVs merbecoviruses are notorious for recombining parts of their genome, especially the spike. Looking more closely, we detected one small part of the RBD where nvHKU5r-CoVs were curiously closer to another bat virus, Q265!
October 28, 2025 at 5:07 AM
The mink HKU5 virus (nvHKU5r-CoV) was sampled in Shendong and seems to be overall closest to different bat HKU5s sampled in P. abramus bats across south and east China. 🦇
When focusing on the spike and RBD, one virus, WZ2, sampled in Zhejiang, is the single closest relative.
October 28, 2025 at 5:07 AM
Arrived in gorgeous cote d' azur just in time for the first day on the European Meeting on Viral Zoonoses!

Aside from enjoying the weather and the wine I'll also be presenting some exciting (and still unpublished) work on novel sarbecovirus discovery! 🍷🏖️🦇
September 20, 2025 at 2:09 PM
Great to be at Elsevier's 19th Vaccine Congress in beautiful Kyoto! 💉💉

An exceptionally important topic to global health, especially in the current political climate...
September 7, 2025 at 7:27 AM
Some very inspiring science at #ismb2025 in Liverpool this week! And great to see lots of Glasgow friends! 😁

Unfortunately had to dip early to get to Oxford! Giving a talk on structural phylo and discussing some exciting projects with @mghafari.bsky.social tomorrow!👀👀
July 24, 2025 at 6:11 PM
Great time in Lisbon so far at @rdrpsummit.bsky.social ! Looking forward to another day of great talks and discussing the future of RNA virus discovery!

+ #ViBioM2025 starting tonight! Can't wait to see lots more friends! 😁😁
May 12, 2025 at 7:28 AM
We tested if the bat virus ancestors could have spread to these cities via bat dispersal and find that it is very unlikely that the ancestors of both SARS-CoV-1 and SARS-CoV-2 reached Guangdong and Wuhan, respectively, solely via dispersal through their bat reservoirs.
May 10, 2025 at 4:46 PM
We find that the closest-inferred ancestors of SARS-CoV-1 likely circulated in western China (Yunnan, Sichuan, or Guizhou), and that of SARS-CoV-2 in Yunnan, China, or Northern Laos, overlapping with contiguous karst and cave landscapes extending through these regions.
May 10, 2025 at 4:46 PM
We show that these viruses have continuously moved across China and Southeast Asia for thousands of years. Their movement ranges are further consistent with the horseshoe bat species richness across these regions.
May 10, 2025 at 4:46 PM
Over recent years of bat sampling, even if we don’t find genomes that are overall more closely related to the human SARS-CoVs, the recCA genetic similarity keeps increasing the more we sample (even for SARS-CoV-1 which emerged 23 years ago).
May 10, 2025 at 4:46 PM
Intriguingly, we find that the closest date when SARS-CoV-2 shared an ancestor with a horseshoe bat virus was only 5 years prior to its emergence, while only about 1 year for SARS-CoV-1.
May 10, 2025 at 4:46 PM
Once we have these NRRs we can perform molecular dating analysis to infer the time when each genome segment of the human SARS-CoVs shared an ancestor with an animal virus (i.e., the closest-inferred ancestor).
May 10, 2025 at 4:46 PM
We inferred recombination breakpoints separately for SARS-CoV-1-like and SARS-CoV-2-like viruses splitting the genomes into NRRs. Interestingly some breakpoint positions were consistent between the two independent sets, suggestive of hotspots of recombination.
May 10, 2025 at 4:46 PM
Sending off some emails with the view of Namsan Tower and soju for the full Seoul experience!

Looking forward to meeting lots of cool people at @recombseq.bsky.social tomorrow and chat all about AI, pLMs, structural predictions and more! 😁

I'll be presenting a poster on our recent work, link 👇
April 23, 2025 at 1:00 PM
Three recent papers uncovered the intricate interactions between bat merbecoviruses and the ACE2 receptor. In
@cp-cellhostmicrobe.bsky.social
we summarise these findings and lay out the plausible evolutionary scenarios they may imply! 🦇🦇

doi.org/10.1016/j.ch...
April 10, 2025 at 7:21 AM
Metagenomics is certainly not the best way to look at intra population viral diversity and we urge future anello studies to prefer long-read sequencing. Look at fig S4 for some more detailed analysis on how read depth relates to our absent features.
January 22, 2025 at 9:51 AM