Jérémy Dufloo

Thrilled to have been awarded a Ramon y Cajal 5-year tenure-track contract to continue working on viral entry (and more!) with @rafa-sanjuan.bsky.social at @i2sysbio.es and @uv.es 😀🎉

Virological characteristics of the SARS-CoV-2 LP.8.1 variant After the rapid spread of the SARS-CoV-2 JN.1 (BA.2.86.1.1) variant,1 several descendant lineages of JN.1, including KP.2 (JN.1.11.1.2),2 KP.3 (JN.1.11.1.3),2 and KP.3.1.1 (JN.1.11.1.3.1.1),3 have eme...

BREAKING🔔 The 50th🎉 paper from G2P-Japan🇯🇵 is out at Lancet Infectious Diseases
@TheLancetInfDis. We elucidated the virological characteristics of SARS-CoV-2 LP.8.1. Please repost🔥
www.thelancet.com/journals/lan...

Dipeptidase 1 is a functional receptor for coronavirus PHEV Coronaviruses of the subgenus Embecovirus include several relevant pathogens such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis ...

Check out our most recent preprint concerning the identification of a protein receptor for the coronavirus #PHEV.
Collaboration with collaboration that we had with @jeremydufloo.bsky.social and Sanjuán’ lab

Human cells have few barriers to prevent the entry of animal viruses A research team from the Institute of Integrative Systems Biology (I2SysBio), a joint centre of the University of Valencia and the Spanish National Research Council (CSIC), asserts that the proteins r...

Press release from the University of Valencia about our recently published article! 📰🗞️

www.uv.es/uvweb/uv-new...

Thanks a lot Spyros! Glad you liked them! 🙏🏻☺️

I'd like to warmly thank all the collaborators involved, especially in the Sanjuán and Rey labs, in particular Ignacio Fernández (not on Bluesky), co-first author of the study! Hope you'll enjoy the read! 📚

Altogether, this highlights the diversity in protein and glycan receptor usage among embecoviruses, and suggests that the embecovirus RBD is a highly versatile structure that can accommodate highly divergent sequences to achieve novel receptor specificities.

Finally, Ignacio used cryoEM to obtain the structure of the PHEV spike ectodomain. This revealed that in contrast to all other embecovirus spikes structurally resolved (OC43, HKU1, MHV), the PHEV spike spontaneously adopts open conformations, allowing interaction with DPEP1.

This allowed us to identify critical residues at the interface. Morevover, this revealed that despite variations in RBD sequences and receptor usage , the structural elements involved in receptor recognition are conserved across embecoviruses.

Ignacio Fernández, from Félix Rey's lab, beautifully obtained the X-ray structure of DPEP1 in complex with the PHEV RBD.

DPEP1 was a PHEV-specific receptor and could not bind other betacoronavirus 1 spikes. This could be explained by large sequence variations between the RBD of PHEV and that of other members of the species, including BCoV or OC43.

Here, we show that contrary to other embecoviruses, the entry of PHEV does not require binding to sialic acid. In contrast, we identify dipeptidase 1 (DPEP1) as a functional PHEV receptor triggering PHEV spike-mediated fusion (entry and cell-cell fusion).

Therefore, sialic acid had long been considered as the only embecovirus receptor. However, the recent discovery that TMPRSS2 acts as the protein receptor of HKU1 revealed a more complex scenario. Whether other embecovirus dually depends on a protein and sialic acid is unknown.

The N-terminal domain (NTD) of the embecovirus spike harbors a conserved glycan-binding site that interacts with sialic acid in HKU1, OC43, BCoV, and PHEV and this interaction is necessary for HKU1, OC43 and BCoV entry.

The betacoronavirus 1 species is the main taxon of the Embecovirus subgenus (Betacoronavirus genus), which includes other relevant viruses such as the human common cold virus HKU1 🤒 and murine hepatitis virus (MHV) 🐁.

In this work, we focused on the betacoronavirus 1 species. It includes ten host-specific viruses such as the porcine hemagglutinating encephalomyelitis virus (PHEV) 🐖 and bovine coronavirus (BCoV) 🐄, but also the human seasonal cold virus OC43 🤒.

Dipeptidase 1 is a functional receptor for coronavirus PHEV Coronaviruses of the subgenus Embecovirus include several relevant pathogens such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis ...

🚨 Preprint alter - bis 🚨

I am thrilled to share our last preprint where we identify and characterize a new coronavirus receptor! 🦠

This work was done in collaboration with the team of Félix Rey at the Institut Pasteur.

A 🧵 below...

www.biorxiv.org/content/10.1...

Identification and characterization of novel bat coronaviruses in Spain The zoonotic transmission of bat coronaviruses poses a threat to human health. However, the diversity of bat-borne coronaviruses remains poorly characterized in many geographical areas. Here, we recov...

🚨 New preprint alert 🚨

We searched for the presence of coronaviruses in >200 bat individuals across Spain 🦠🦇. We recovered 6 complete coronavirus genomes, including 3 novel species. One of them could use bat and human ACE2 for entry.

www.biorxiv.org/content/10.1...

Thanks! 🙏🏻

I'd like to warmly thank everyone in Rafael Sanjuán's lab involved in this project! 🙏😃 I hope you'll enjoy the read, and don't hesitate to reach out if you're interested in any of the pseudotypes we generated! 😉

Altogether, our results suggest that post-entry stages of the infection cycle, as well as epidemiological and ecological factors, may be more critical determinants of viral zoonosis than entry.

We also tested the role of non-protein factors (i.e. sialic acids and heparan sulfates) in the entry of around 80 human-infective pseudotypes.

In contrast, we showed that some host factors acted as broad-range determinants of viral entry. For example, the basal levels of IFITMs correlated negatively with the infectivity of most viral pseudotypes.

We first focused on known viral receptors and showed that the infectivity of some, but not all, pseudotypes correlated with receptor expression. For many viruses, the availability of specific cell-surface receptors is therefore not the main factor limiting viral entry.

Since several transcriptomic and proteomic datasets are available for the NCI-60 panel, we could compare gene expression and pseudotype infectivity data to explore the molecular determinants of animal virus entry into human cells.

Using this dataset and 81 features on viral taxonomy, host, RBP and the cell type being challenged, we used gradient boosting to explore the predictability of RBP-mediated human cell internalization. >75% of the total 5,202 RPB–cell combinations tested were correctly predicted.

Suprisingly, >80% of the tested viral species could enter into at least one human cell line. However, this varied strongly across viral families, with coronaviruses showing the strongest interspecies barrier at the entry stage.

Given the zoonotic risk posed by enveloped RNA viruses and the importance of viral entry in cross-species transmission, we used viral pseudotyping to test whether the RBPs of 102 animal viruses from 14 families could allow entry into >50 human cell lines from the NCI-60 panel.

Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors - Nature Microbiology Functional systematic pseudotype virus-based analysis of the ability of diverse animal viruses to enter into a panel of well-characterized human cell lines shows a broad compatibility between animal v...

To get 2025 off to a good start, I'm delighted to share with you our study published today in @naturemicrobiol.bsky.social 🎉 We studied the ability of the receptor-binding proteins (RBP) of >100 animal viruses to mediate entry into human cells. A short thread below.
www.nature.com/articles/s41...

We first focused on known viral receptors and showed that the infectivity of some, but not all, pseudotypes correlated with receptor expression. For many viruses, the availability of specific cell-surface receptors is therefore not the main factor limiting viral entry.