A5019210804- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Natural product bioactivities and synthesis
- Traditional and Medicinal Uses of Annonaceae
- Viral gastroenteritis research and epidemiology
- Pancreatic function and diabetes
- Diabetes Management and Research
- RNA and protein synthesis mechanisms
- Phytochemistry and Biological Activities
- HIV Research and Treatment
- Hepatitis C virus research
- Plant biochemistry and biosynthesis
- Viral Infections and Immunology Research
- Insect symbiosis and bacterial influences
- Enzyme Catalysis and Immobilization
- Microbial Natural Products and Biosynthesis
- RNA modifications and cancer
- Computational Drug Discovery Methods
- Diabetes Treatment and Management
- Malaria Research and Control
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Bioactive Natural Diterpenoids Research
- Flavonoids in Medical Research
- CRISPR and Genetic Engineering
Architecture et Fonction des Macromolécules Biologiques
2014-2025
Aix-Marseille Université
2011-2025
Centre National de la Recherche Scientifique
2009-2025
University of New Caledonia
2012
Structural Genomics Consortium
2008
Institut de Biologie Structurale
2006
Abstract The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). recently entered phase III clinical trials for the treatment of COVID-19. Once in cells, is converted into its triphosphate form, AT-9010, that presumably targets viral RNA-dependent RNA polymerase (RdRp, nsp12), incorporation RNA. Here we report 2.98 Å cryo-EM structure SARS-CoV-2 nsp12-nsp7-nsp8 -RNA complex, showing AT-9010 bound at three sites...
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), is a global threat to human health. Using multidisciplinary approach, we identified and validated hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load multiple orders magnitude synergizes with remdesivir in vitro. Mechanistically, showed that not only inhibits...
Dengue virus is the world's most prevalent human pathogenic arbovirus. There currently no treatment or vaccine, and solutions are urgently needed. We previously demonstrated that biflavonoids from <i>Dacrydium balansae</i>, an endemic gymnosperm New Caledonia, potent inhibitors of NS5 RNA-dependent RNA polymerase. Herein we describe structure-activity relationship study 23 compounds: <i>D. balansae</i> (<b>1</b>–<b>4</b>) araucarioides</i> (<b>5</b>–<b>10</b>), hexamethyl-amentoflavone...
An in vitro screening of New Caledonian plants allowed the selection several species with a significant dengue virus NS5 RNA-dependent RNA polymerase (RdRp) inhibiting activity. The chemical investigation Cryptocarya chartacea led to isolation series new mono- and dialkylated flavanones named chartaceones A-F (1-6), along pinocembrin. They were isolated as racemic mixtures characterized using extensive one- two-dimensional NMR spectroscopy. Four diastereomers chartaceone A (1) separated...
In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts madagascan plants was performed in virus-cell-based assay for CHIKV, DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark Flacourtia ramontchi selected its significant activity both assays. Six new phenolic glycosides, named flacourtosides A–F (1–6), glycosides itoside H, xylosmin, scolochinenoside D,...
Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, lid, which normally undergoes conformational changes only upon addition lipids or amphiphiles. Structures PL with their lids in open and functional conformation have required cocrystallization Here we report two crystal structures wild-type unglycosylated human lipase-related protein 2 (HPLRP2) lid an absence These solved independently are strikingly similar, some residues being poorly defined...
Recombinant human pancreatic lipase-related protein 2 (rHPLRP2) was produced in the protease A-deficient yeast Pichia pastoris. A major with a molecular mass of 50 kDa purified from culture medium using SP-Sepharose and Mono Q chromatography. The found to be highly sensitive proteolytic cleavage peptide bond lid domain. process occurring affected both lipase phospholipase activities rHPLRP2. substrate specificity nonproteolyzed rHPLRP2 investigated pH-stat monomolecular film techniques...
In order to find new molecules for antiviral drug design, we screened 102 ethyl acetate extracts from New-Caledonian flora activity against the dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of Dacrydium balansae, which strongly inhibited DV-NS5, was submitted bioguided fractionation. Four biflavonoids (1–4), three sterols (5–7), and two stilbene derivatives (8–9) were identified evaluated their potential on DV-NS5 RdRp. Biflavonoids appeared be potent inhibitors...
Protein–protein interactions (PPIs) represent an enormous source of opportunity for therapeutic intervention. We and others have recently pinpointed key rules that will help in identifying the next generation innovative drugs to tackle this challenging class targets within decade. used these design oriented chemical library corresponding a set diverse "PPI-like" modulators with cores identified as privileged structures therapeutics. In work, we purchased resulting 1664 structurally compounds...
From a set of 292 Euphorbiaceae extracts, the use molecular networking (MN)-based prioritization approach highlighted three clusters (MN1–3) depicting ions from bark extract Codiaeum peltatum. Based on their putative antiviral potential and structural novelty, MS-guided purification compounds present in MN1 MN2 afforded two new daphnane-type diterpenoid orthoesters (DDO), codiapeltines A (1) B (2), actephilols (3) C (4), four known 1,4-dioxane-fused phenanthrene dimers (5–8). The structures...
Following a biological screening using dengue replicon virus-cell-based assay, Diospyros carbonaria AcOEt extract was investigated, affording six known lupane-type triterpenoids endowed with anti-DENV-2 NS5 polymerase activity. The study of the associated microbial community this species permitted us to identify 38 endophytes belonging five different orders. Nine out these strains showed significant activity on assay. chemical investigation most active one, Phomopsis sp. SNB-LAP1-7-32, led...
Abstract The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), is a global threat to human health. Using multidisciplinary approach, we identified and validated hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load multiple orders magnitude synergizes with remdesivir in vitro . Mechanistically, showed that...
Summary How viruses from the Coronaviridae family initiate viral RNA synthesis is unknown. Here we show that SARS-CoV-1 and −2 Ni dovirus R dRp- A ssociated N ucleotidyltransferase (NiRAN) domain on nsp12 uridylates cofactor nsp8, forming a UMP-Nsp8 covalent intermediate subsequently primes poly(A) template; protein-priming mechanism reminiscent of Picornaviridae enzymes. In parallel, RdRp active site synthesizes pppGpU primer, which (-)ssRNA at precise genome-poly(A) junction. The guanosine...