Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

The enzymes for genome size increase and maintenance of large (+)RNA viruses (2021) Ferron F, Sama B, Decroly E, Canard B . Trends Biochem Sc in press PMID:34172362
System-oriented optimization of multi-target 2,6-diaminopurine derivatives: Easily accessible broad-spectrum antivirals active against flaviviruses, influenza virus and SARS-CoV-2 (2021) Vicenti I, Martina MG, Boccuto A, De Angelis M, Giavarini G, Dragoni F, Marchi S, Trombetta C M, Crespan E, Maga G, Eydoux C, Decroly E, Montomoli E, Nencioni L, Zazzi M, Radi M. Eur J Med Chem In press PMID:34273661
Structure and sequence requirements for RNA capping at the Venezuelan Equine Encephalitis Virus RNA 5'-end (2021) Ortega Granda O, Valle C, Shannon A, Decroly E, Canard B, Coutard B, Rabah N. J Virol In press PMID:34011549
Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir (2021) Lo HS, Hui KPY, Lai HM, Khan KS, Kaur S, Huang J, Li JHZ, Chan AKN, Cheung HY, Ng KC, Ho JCW, Chen YW, Ma B, Cheung PMH, Shin D, Wang K, Lee MH, Selisko B, Eydoux C, Guillemot JC, Canard B, Wu KP, Liang PH, Dikic I, Zhong Zuo, Chan F K. L, Hui D S. C., Mok V C. T., Wong KB, Ko H, Shen Aik W, Chi Wai Chan M, Ng WL . ACS Cent Sci 7 792-802 PMID:34075346
The WHO mission report struggles to trace the origins of the SARS-CoV-2 epidemic (tribune) (2021) Decroly E, Claverie JM, Canard B. Virologie (Montrouge) In press PMID:34112630
The methyltransferase domain of the Respiratory Syncytial Virus L protein catalyzes cap N7 and 2 O methylation (2021) Sutto-Ortiz P, Tcherniuk S, Ysebaert N, Abeywickrema P, Noel M, Decombe A, Debart F, Vasseur JJ, Canard B, Roymans D, Rigaux P, Eleouet JF, Decroly E. Plos Pathogens May 6 PMID:33956914

...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.