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Reposted by Franck Touret

IRD @ird-fr.bsky.social · 15/06/2026

🦠 Fièvre de la Vallée du Rift, virus de Crimée-Congo, hantavirus… Face à ces fièvres hémorragiques virales, des chercheurs de l'Unité des Virus Emergents (UVE) ont misé sur une stratégie de réponse directe à l'épidémie : le repositionnement de médicaments. Plus d'infos: lemag.ird.fr/fr/combattre...

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Reposted by Franck Touret

Mathieu M.J.E. Rebeaud @chercheurjuteux.com · 17/02/2026

How Can Pharmacology Help Us Overcome the Challenges of Drug Repositioning as Antivirals to Treat Emerging Pathogens? The Example of Covid‐19 Revue entre Paris, Dijon, Marseille avec @franckdrtourte.bsky.social et le juteux @nathanpsmad.bsky.social ascpt.onlinelibrary.wiley.com/doi/10.1111/...

ascpt.onlinelibrary.wiley.com

How Can Pharmacology Help Us Overcome the Challenges of Drug Repositioning as Antivirals to Treat Emerging Pathogens? The Example of Covid‐19

Pharmacological pitfalls and challenges in drug repurposing for emerging pathogens: lessons from COVID-19.

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Franck Touret @franckdrtourte.bsky.social · 20/05/2025

Yes on suit ça de près aussi 😁

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Franck Touret @franckdrtourte.bsky.social · 12/05/2025

While not a replacement for standard antiviral screening, this 3D model offers valuable insights into viral replication, pathogenicity, and host-pathogen interactions.

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Franck Touret @franckdrtourte.bsky.social · 12/05/2025

Our research findings: RVFV and PIRV replicated in the liver spheroids; AHFV and YFV did not. Broad-spectrum antivirals (favipiravir, nitazoxanide, ribavirin, galidesivir) showed activity, though higher doses were often needed versus traditional 2D models.

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Franck Touret @franckdrtourte.bsky.social · 12/05/2025

Haemorrhagic fever viruses remain a major global health threat—highly lethal, with limited therapeutic options. In our recent study, we explored a 3D human liver spheroid model to evaluate its potential for antiviral assessment against 4 BSL-3 viruses: AHFV, YFV, PIRV, RVFV.

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Franck Touret @franckdrtourte.bsky.social · 12/05/2025

Just published in Antiviral research! 3D Liver Spheroids in the Fight Against Haemorrhagic Fever Viruses t.co/FuxQ76acrg @ird-fr.bsky.social @univ-amu.fr @insermpacacorse.bsky.social

t.co

https://doi.org/10.1016/j.antiviral.2025.106188

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Franck Touret @franckdrtourte.bsky.social · 24/02/2025

On a des antiviraux efficaces: paxlovid ( Nirmatrelvir) et xocova ( ensitrelvir) on sait comment faire un vaccin ou des anticorps thérapeutiques rapidement. On est entouré de virus à la capacité zoonotique et celui là se rajoute juste à la longue liste mais tkt a l UVE on est là pour ça 😉

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Franck Touret @franckdrtourte.bsky.social · 24/02/2025

Oui c’est uniquement l’entrée mais d’autre facteurs rentrent en ligne de compte pour un changement d’hôte et une zoonose( par exemple la capacité du virus à échapper à la réponse immune). De plus avec le recul un coronavirus est moins inquiétant que d’autres familles virales 1/2

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

Moreover, pharmacokinetic modeling suggests promising druggability for these compounds. These results position OM1260 and HR-568 as strong candidates for further development, potentially paving the way for the first curative treatments for enteroviral infections.

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

Docking studies provided insights into their structure-activity relationships, while time-of-drug addition assays revealed that these inhibitors act early in the viral replication cycle.

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

This led to the discovery of two promising broad-spectrum inhibitors, OM1260 and HR-568. Both inhibitors show micromolar activity against multiple enterovirus types (EV-A71, E30, and CVA24), with EC50 values ranging from 0.4 μM to 4.38 μM, depending on the virus strain and cell line.

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

Our consortium has made an exciting step forward in the fight against these viruses. After developing initial EV-A71 inhibitors, we optimized their structure through iterative chemical modifications to enhance their activity and broaden their spectrum.

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

Despite their significant impact, there are currently no commercial curative treatments available.

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Franck Touret @franckdrtourte.bsky.social · 14/02/2025

🔬 New Research Breakthrough: Broad-Spectrum Inhibitors for Enteroviruses🦠Enteroviruses (EV) are a diverse group of viruses that can cause a range of illnesses, from mild fever to severe neurological complications.

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Franck Touret @franckdrtourte.bsky.social · 30/01/2025

Our research underscores the growing importance of advanced 3D models in virology and drug development. This tool could help accelerate the identification of new therapies for HFVs and improve our understanding of their mechanisms.

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Franck Touret @franckdrtourte.bsky.social · 30/01/2025

While this model offers valuable insights, it’s not a replacement for standard selection steps in antiviral drug development but could play a key role in understanding viral pathogenicity and host-pathogen interactions.

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Franck Touret @franckdrtourte.bsky.social · 30/01/2025

Key findings : RVFV and PIRV were able to replicate in the spheroids, while the orthoflaviviruses did not show replication. Antiviral compounds like favipiravir, nitazoxanide, ribavirin, and galidesivir demonstrated activity, though higher doses were required in 3D models compared to 2D cultures.

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Franck Touret @franckdrtourte.bsky.social · 30/01/2025

Our latest study explores the use of a 96-well liver spheroid model composed of human primary cells to assess the antiviral activity of key compounds against four BSL-3 HFVs: Alkhumra haemorrhagic fever virus (AHFV), yellow fever virus (YFV), Pirital virus (PIRV), and Rift Valley fever virus (RVFV).

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Franck Touret @franckdrtourte.bsky.social · 30/01/2025

🚨 New Insights on Hemorrhagic Fever Viruses & 3D Cell Culture Models 🦠 In the ongoing battle against hemorrhagic fever viruses (HFVs), the development of effective antiviral strategies remains a critical challenge.

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Franck Touret @franckdrtourte.bsky.social · 05/11/2024

C’est énorme! Faut faire une grosse fiesta!

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Franck Touret @franckdrtourte.bsky.social · 05/11/2024

C’est super cool de pouvoir tracer son histoire aussi loin!

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Franck Touret @franckdrtourte.bsky.social · 05/11/2024

Vous avez toujours été en Suisse ou vous avez bougé depuis ces 600 dernières années?

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Franck Touret @franckdrtourte.bsky.social · 31/10/2024

« Pas sérieux » c’est gentiment dit j’aurais été moins poli 😉

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

What is the sensitivity of these strains to mosnodenvir in vivo ? why did this mutation emerge repeatedly ? and that's the end of the thread (15/15)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

Et voilà ! Clearly this is not the end of the story though, several questions remain open at this stage and would allow us to better appreciate the current risk associated with the circulation of NS4B:V91A-carrying strains (14/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

A key takeaway from this work is the importance of monitoring the genomes of circulating dengue viruses to ensure that it is properly administered against susceptible viral strains.(13/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

In summary, we show that DENV strains with low sensitivity to mosnodenvir have circulated, still circulate, and may cause epidemics but still represent a minor fraction of circulating strains at present.(12/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

the cases associated with the French Caribbean epidemic lineage constitute only a minor fraction, less than 1%, of the total number of cases reported in 2023.Mosnodenvir therefore remains a very promising compound and a tool of choice in the fight against dengue fever.(11/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

Finally, although this study demonstrates the epidemic circulation of viruses with low susceptibility to mosnodenvir, we have estimated -based on case numbers and the sequence data available at the time of the study- that (10/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

To control the breadth of the effect of NS4B:V91A we observed in strains from DENV2 genotype II, we inserted the mutation into DENV strains belonging to different serotypes and genotypes, confirming a low sensitivity to mosnodenvir in all our mutants.(9/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

We then assessed the past and present circulation of strains carrying the mutation, using publicly available DENV genome data available on genbank. We found that NS4B:V91A strains have emerged repeatedly over the last 30 years, in the serotypes 2 and 3 of DENV.(8/)

V91A emergence events within DENV-2 (A) and DENV-3 (B) serotypes.

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

As the effect of this mutation had never been described in a ‘wild’ virus, we tested the sensitivity of viruses collected to mosnodenvir and to JNJ A07 a similar molecule. We found a drastic reduction in activity to both mosnodenvir and JNJ A07, with an EC50 reaching µM . (7/)

Strategy used to characterize the V91A resistance mutation in vitro using either strains from the epidemic or strains generated using reverse genetics.

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

As part of its routine genomic surveillance, the French National Reference Center for arboviruses identified that NS4B:V91A was present in all the virus genomes from a dengue epidemic that began in 2023 in the French Caribbean Islands. (6/)

V91A is present in the entire epidemic clade and its closest phylogenetic ancestor

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

A point of concern however, is that some mutations in the NS4B protein can decrease the sensitivity of DENV strains to mosnodenvir, including NS4B:V91A, which is present in a small proportion of dengue strains circulating worldwide (5/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

Alongside vaccines, antivirals have also been developed for many years, including mosnodenvir (JNJ-1802). This drug candidate is now finishing its phase 2 clinical trial at 37 sites around the world. (4/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

One of the major strategies used to combat dengue fever is vaccination, but the genetic and serotypic diversity of the virus and the severe clinical forms that can occur upon reinfection have hindered the development of a safe and effective vaccine. (3/)

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Franck Touret @franckdrtourte.bsky.social · 10/10/2024

Almost 1/2 of the world's population is currently at risk of contracting dengue fever, a mosquito-borne disease that mainly affects tropical and subtropical areas . Dengue cases has risen in recent years, from 3.2 M cases worldwide in 2015 to more than 10 M since January (2/)

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