Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

Design, synthesis and discovery of novel N,N'-carbazoyl-aryl-urea inhibitors of Zika NS5 methyltransferase and virus replication. (2019) Spizzichino S, Mattedi G, Lauder K, Valle C, Aouadi W, Canard B, Decroly E, Kaptein SJF, Neyts J, Graham C, Sule Z, Barlow DJ, Silvestri R, Castagnolo D. ChemMedChem in press PMID:31805205
Structure of the Respiratory Syncytial Virus Polymerase Complex. (2019) Gilman MSA, Liu C, Fung A, Behera I, Jordan P, Rigaux P, Ysebaert N, Tcherniuk S, Sourimant J, Eleouet JF, Sutto-Ortiz P, Decroly E, Roymans D, Jin Z, McLellan JS. Cell 179 193-204 PMID:31495574
The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity. (2019) Ogando NS, Ferron F, Decroly E, Canard B, Posthuma CC, Snijder EJ. Front Microbiol 10 1813 PMID:31440227
Structure and oligomerization state of the C-terminal region of the Middle East respiratory syndrome coronavirus nucleoprotein. (2019) Nguyen THV, Lichiere J, Canard B, Papageorgiou N, Attoumani S, Ferron F, Coutard B. Acta Crystallogr D Struct Biol 75 8-15 PMID:30644840
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

...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.