Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure. (2018) B. Martin B. Coutard T. Guez G.C. Paesen B. Canard F. Debart J.J. Vasseur J.M. Grimes E. Decroly. Nucleic Acids Res https://doi.org/10.1093/nar/gky637 PMID:0
Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors. (2018) Halby L, Marechal N, Pechalrieu D, Cura V, Franchini DM, Faux C, Alby F, Troffer-Charlier N, Kudithipudi S, Jeltsch A, Aouadi W, Decroly E, Guillemot JC, Page P, Ferroud C, Bonnefond L, Guianvarc'h D, Cavarelli J, Arimondo PB. Philos Trans R Soc Lond B Biol Sci 373 PMID:29685976
Filovirus proteins for antiviral drug discovery: Structure/function of proteins involved in assembly and budding. (2018) Martin B, Reynard O, Volchkov V, Decroly E. Antiviral Res 150 183-192 PMID:29305306
Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA. (2018) Ferron F, Subissi L, Silveira De Morais AT, Le NTT, Sevajol M, Gluais L, Decroly E, Vonrhein C, Bricogne G, Canard B, Imbert I. Proc Natl Acad Sci U S A 115 E162-E171 PMID:29279395
Toscana virus nucleoprotein oligomer organization observed in solution. (2017) Baklouti A, Goulet A, Lichiere J, Canard B, Charrel RN, Ferron F, Coutard B, Papageorgiou N. Acta Crystallogr D Struct Biol 73 650-659 PMID:28777080
Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay. (2017) Aouadi W, Eydoux C, Coutard B, Martin B, Debart F, Vasseur JJ, Contreras JM, Morice C, Querat G, Jung ML, Canard B, Guillemot JC, Decroly E. Antiviral Res 144 330-339 PMID:28676301

...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.