A5039783946- Mosquito-borne diseases and control
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
- Animal Virus Infections Studies
- RNA modifications and cancer
- Hepatitis C virus research
- Plant Virus Research Studies
- Insect symbiosis and bacterial influences
- interferon and immune responses
- Virology and Viral Diseases
- Virus-based gene therapy research
- Respiratory viral infections research
- Malaria Research and Control
- Enzyme Structure and Function
- RNA Research and Splicing
- HIV/AIDS Research and Interventions
- RNA Interference and Gene Delivery
Architecture et Fonction des Macromolécules Biologiques
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Aix-Marseille Université
2016-2025
Jena Bioscience (Germany)
2022
Inserm
2018
École Normale Supérieure de Lyon
2018
Centre International de Recherche en Infectiologie
2018
Université Claude Bernard Lyon 1
2018
Virologie et Pathologies Humaines
2018
Helmholtz-Zentrum Berlin für Materialien und Energie
2012
Replication of the giant RNA genome severe acute respiratory syndrome (SARS) coronavirus (CoV) and synthesis as many eight subgenomic (sg) mRNAs are mediated by a viral replicase-transcriptase outstanding complexity that includes an essential endoribonuclease activity. Here, we show CoV replicative machinery, unlike other viruses, also uses exoribonuclease (ExoN) activity, which is associated with nonstructural protein (nsp) 14. Bacterially expressed forms SARS-CoV nsp14 were shown to act on...
Significance The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East highlight the potential lethality zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess largest known RNA virus genomes encode a complex replication machinery consisting 16 viral nonstructural proteins (nsps). Our study reveals that SARS-coronavirus polymerase (nsp12) needs to associate with nsp7 nsp8 activate its...
Significance Emerging coronaviruses (CoVs; severe acute respiratory syndrome-CoV and Middle East syndrome-CoV) pose serious health threats globally, with no specific antiviral treatments available. These viruses are able to faithfully synthesize their large genomic RNA. We report, however, that main RNA polymerase, nsp12, is not accurate. To achieve accuracy, CoVs have acquired nsp14, a bifunctional enzyme methylate the viral cap [methyltransferase (MTase)] excise erroneous mutagenic...
Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, member of the Flavivirus genus, includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from virus bifunctional contains 900 amino acids. S-adenosyl methionine transferase activity resides within its N-terminal domain, residues 270 to form RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins...
SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set mRNAs, which presumably are capped at their 5' end and direct all viral proteins in infected cell. Sixteen non-structural (nsp1 to nsp16) constitute an unusually large replicase complex, includes two methyltransferases putatively involved mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed nsp14, whereas nsp16 has been...
Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a (nucleoside-2′-O)-methyltransferase only active the presence of its activating partner nsp10. We report nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to through ∼930 Å2...
The replication/transcription complex of severe acute respiratory syndrome coronavirus is composed at least 16 nonstructural proteins (nsp1–16) encoded by the ORF-1a/1b. This includes replication enzymes commonly found in positive-strand RNA viruses, but also a set RNA-processing activities unique to some nidoviruses. nsp14 protein carries both exoribonuclease (ExoN) and (guanine-N7)-methyltransferase (N7-MTase) activities. ExoN activity ensures yet-uncharacterized function virus life cycle...
Abstract The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used treatment of several diseases. We demonstrate here that Favipiravir predominantly exerts an effect through lethal mutagenesis. SARS-CoV RdRp complex at least 10-fold more active than any...
The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent COVID-19, is global and unprecedented. Although remdesivir has recently been approved by FDA to treat SARS-CoV-2 infection, no oral antiviral available for outpatient treatment.
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 recently identified etiological agent of the severe acute respiratory syndrome (SARS) belongs to Coronaviridae (CoV), a family viruses replicating by poorly understood mechanism. Here, we report crystal structure at 2.7-Å resolution nsp9, hitherto uncharacterized subunit SARS-CoV replicative polyproteins. We show that nsp9 is single-stranded RNA-binding protein displaying previously unreported, oligosaccharide/oligonucleotide fold-like fold. presence this type has not been detected in...
The nucleoprotein of measles virus consists an N-terminal moiety, N(CORE), resistant to proteolysis and a C-terminal N(TAIL), hypersensitive not visible as distinct domain by electron microscopy. We report the bacterial expression, purification, characterization N(TAIL). Using nuclear magnetic resonance, circular dichroism, gel filtration, dynamic light scattering, small angle x-ray we show that N(TAIL) is structured in solution. Its sequence spectroscopic hydrodynamic properties indicate...