A5030802871- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Biochemical and Molecular Research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Hepatitis C virus research
- Viral Infections and Vectors
- Enzyme Structure and Function
Inserm
2016-2024
Hôpital Saint-Louis
2024
Centre National de la Recherche Scientifique
2016-2024
Institut de recherche Saint-Louis
2024
Université Paris Cité
2016-2024
Institut Cochin
2016-2023
Université Paris-Est Créteil
2019
Mutabilis (France)
2013-2018
Délégation Paris 5
2016
Sorbonne Paris Cité
2016
LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets integration HIV in actively transcribed gene regions chromatin. A recently developed class IN allosteric inhibitors can inhibit LEDGF-IN interaction.
Alphaviruses, such as chikungunya virus (CHIKV), are mosquito-borne viruses that represent a significant threat to human health due the current context of global warming. Efficient alphavirus infection relies on activity non-structural protein 3 (nsP3), puzzling multifunctional molecule whose role in remains largely unknown. NsP3 is component plasma membrane-bound viral RNA replication complex (vRC) essential for amplification and also found large cytoplasmic aggregates unknown function
HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on viral protein with host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of IN to severely perturb maturation particles.
Argonaute (Ago) proteins associate with microRNAs (miRNAs) to form the core of RNA-induced silencing complex (RISC) that mediates post-transcriptional gene target mRNAs. As key players in anti-viral defense, Ago are thought have ability interact human immunodeficiency virus type 1 (HIV-1) RNA. However, role this interaction regulating HIV-1 replication has been debated. Here, we used high throughput sequencing RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) explore between Ago2...
HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers HIV preintegration complex to host genome enabling integration. Recently a new class of IN inhibitors was described, IN-LEDGF allosteric (INLAIs). Designed interfere interaction during integration, major impact these surprisingly found on virus maturation, causing reverse transcription defect in target cells.Here we describe MUT-A compound as genuine INLAI an original chemical structure based type scaffold,...
Abstract LEDGF/p75 (LEDGF) main cellular cofactor of HIV-1 integrase (IN), acts as tethering factor to target integration HIV in actively transcribed genes. Recently a class IN inhibitors based on inhibition LEDGF-IN interaction has been developed. We describe here new series IN-LEDGF allosteric (INLAIs), with potent anti-HIV-1 activity the one-digit nanomolar range. These compounds inhibited while enhancing IN-IN aberrant multimerization by mechanism. Compounds this were fully active...
Abstract The liver-specific micro-RNA-122 (miR-122) is required for the replication of hepatitis C virus (HCV). direct interaction between miR-122 and 5’ untranslated region HCV genome promotes viral protects RNA from degradation. Because its own substrate replication, infected cells are submitted to sequestration increasing levels global de-repression host mRNA targets. Whether how regulates maturation create an environment favorable remains unexplored. We discovered that Akt-dependent...