Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

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 in press PMID:28676301
Antiviral activity of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones against chikungunya virus targeting the viral capping nsP1. (2017) Gigante A, Gomez-SanJuan A, Delang L, Li C, Bueno O, Gamo AM, Priego EM, Camarasa MJ, Jochmans D, Leyssen P, Decroly E, Coutard B, Querat G, Neyts J, Perez-Perez MJ. Antiviral Res. PMID:28619679
Biochemical principles and inhibitors to interfere with viral capping pathways. (2017) Decroly E, Canard B. Curr Opin Virol 24 87-96 PMID:28527860
Substrate selectivity of Dengue and Zika virus NS5 polymerase towards 2'-modified nucleotide analogues. (2017) Potisopon S, Ferron F, Fattorini V, Selisko B, Canard B. Antiviral Res 140 25-36 PMID:28041959
Filovirus proteins for antiviral drug discovery: Structure/function bases of the replication cycle. (2017) Martin B, Canard B, Decroly E. Antiviral Res 141 48-61 PMID:28192094

...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.