Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

Metal chelators for the inhibition of the lymphocytic choriomeningitis virus endonuclease domain (2019) Saez-Ayala M, Laban Yekwa E, Mondielli C, Roux L, Hernandez S, Bailly F, Cotelle P, Rogolino D, Canard B, Ferron F, Alvarez K. Antiviral Res. 162 79-89 PMID:30557576
Identification of a new natural gastric lipase inhibitor from star anise. (2019) Kamoun J, Rahier R, Sellami M, Koubaa I, Mansuelle P, Lebrun R, Berlioz-Barbier A, Fiore M, Alvarez K, Abousalham A, Carriere F, Aloulou A. Food Funct 10 469-478 PMID:30632597
C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system. (2019) Jais PH, Decroly E, Jacquet E, Le Boulch M, Jais A, Jean-Jean O, Eaton H, Ponien P, Verdier F, Canard B, Goncalves S, Chiron S, Le Gall M, Mayeux P, Shmulevitz M. Nucleic Acids Res in press PMID:30726994
Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay. (2019) Ferreira-Ramos AS, Li C, Eydoux C, Contreras JM, Morice C, Querat G, Gigante A, Perez Perez MJ, Jung ML, Canard B, Guillemot JC, Decroly E, Coutard B. Antiviral Res in press PMID:30639438
FTSJ3 is an RNA 2'-O-methyltransferase recruited by HIV to avoid innate immune sensing. (2019) Ringeard M, Marchand V, Decroly E, Motorin Y, Bennasser Y. Nature in press PMID:30626973
[Ebola virus L protein harbors a new enzymatic activity involved in the internal methylation of RNAs]. (2018) Martin B, Valle C, Coutard B, Canard B, Debart F, Decroly E. Med Sci (Paris) 34 919-921 PMID:30526829

...All publications

Our team seeks to unravel the molecular mechanisms of emerging viruses by characterizing the structures and the enzymatic activities of proteins forming the viral replication and transcription complex. These studies are a prerequisite for the development of specific inhibitors of these enzymes and should allow the development of new antiviral strategies.

RNA viruses are often associated with the emergence of infectious diseases. Among the best known, epidemics related to Ebola, SARS coronavirus and MERS, chikungunya or dengue virus illustrate the worldwide public health concern related to viral infections. The team "Viral replicase: structure, mechanism and drug-design" characterizes enzymes and proteines from emerging viruses involved in the replication of their genome and transcription of their messenger RNAs. These enzymes are associated in a replication/transcription complex (RTC). Our studies focus not only on viral polymerases that are at the heart viral replication, but also on the enzymes involved in RNA modifications such as capping and proofreading and proteins involved in the regulation of replication. Beyond the study of the RTC, we are also interested in the interplay of these enzymes with the innate immunity defence mechanism of the cell. The viral replication proteins are privileged antiviral targets and understanding of their structure and function is essential for the design of antiviral molecules with a high potential. To support these research projects, the lab benefits from the support of an inhibitor-screening platform (PCML) and a platform dedicated to the expression of recombinant viral proteins.