VHC - Virus Hépatologie Cancer | HENRI MONDOR

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    Slim FOURATI                                                                 

   PhD, MCU-PH, MD,                                                   
   slim.fourati@aphp.fr                                               

Epidemiology and virology of acute respiratory infections and resistance of respiratory syncytial virus to new antivirals



Thematic

Our team is working on the development of novel antiviral therapeutic approaches targeting respiratory pathogens such as respiratory syncytial virus (RSV), parainfluenza virus, metapneumovirus and coronavirus. In this context, the group is conducting clinical research and participates in numerous translational research projects within the multidisciplinary framework of the research team. On the strength of its innovative approaches including viral metagenomics, the virology team aims at unraveling:

  • The role of Respiratory Syncytial Virus (RSV) infection in severe respiratory diseases in patients attending the emergency department and the influence of there immune system on the infection.
  • The effect of ribavirin in RSV quasispecies evolution in immune compromised patients, or patients requiring hospitalization in intensive care units. This project aims to characterize temporal evolution of viral quasispecies by full-length genome sequence analysis by means of shotgun metagenomics based on deep sequencing in patients failing ribavirin treatment

The arrival of new antivirals against RSV and metapneumovirus is creating the need for significant investment in the development of innovative techniques to search for amino acid substitutions associated with resistance (polymerase gene L or fusion gene F); and to determine the phenotypic consequences of these substitutions on sensitivity to antivirals.

Phenotypic testing for RSV resistance to novel antiviral agents

Several prototypes are used:

  • ATCC Long strain VR-26
  • Clinical strains
  • Subgenomic replicon (APATH), minireplicon

Phenotypic sensitivity of RSV to antivirals has recently been established in the laboratory. The inhibition of viral replication is evaluated by measuring the luciferase activity (replicon) or plaque reduction assays (VR-26 strain, clinical strains) in the presence of various concentrations of antivirals and at various post-treatment times. The level of resistance is measured by assessing the EC 50, defined as the antiviral concentrations that inhibit viral replication by 50%.

Development of novel antiviral approaches targeting RSV and metapneumovirus

The developed tools are used to evaluate the antiviral efficacy of original compounds that are tested in the research group.


Team Members

  • Nazim Ahnou, Research Ingeneer
  • Abdelhakim Ahmed-Belkacem, INSERM Research Ingeneer
  • François Berry, PhD
  • Sabah Hamadat, Research Ingeneer

Collaborations

  • Astrid Vabret, PU-PH Virology Department - Caen Hospital
  • Marie-Anne Rameix-Welti, MCU-PH University of Versailles