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 🇯🇵


💻🦠🏳️‍🌈
😍😍🍻🍻
November 16, 2025 at 8:42 AM
thanks Martin!
November 16, 2025 at 8:41 AM
thanks Philippe! that'd be great!
November 16, 2025 at 8:41 AM
thanks Mart! It'll great to be there! 😁
November 16, 2025 at 8:41 AM
thank you Cadhla!!
November 16, 2025 at 8:40 AM
thank you Milot!
November 16, 2025 at 8:40 AM
The Antigen Evolution & Design lab will focus on using AI-enabled methods to uncover molecular interactions within antigen protein sequences and structures. This approach will be used for designing better, broader immunity vaccines.

More info will follow soon, stay tuned! 😁😁
November 15, 2025 at 6:42 AM
Big thanks to Vic Jefferson, Nick Catanzaro, Ralph Baric and Michael Letko @fviromics.bsky.social and big congrats to
@jarelelgin.bsky.social
, our talented PhD student who led the work!! 🥳🥳
October 28, 2025 at 5:07 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
Lastly we did comprehensive recombination and molecular dating analysis to explore the origins of this nvHKU5r-CoV. Our findings support that the virus transmitted from bats to mink within the last decade, consistent with an expansion of mink fur farming in China.
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
Then we asked, since ACE2 ortholog usage seems to shift quite easily in these viruses, could nvHKU5r-CoV potentially use human ACE2?
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