Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography (2020) Ferreira-Ramos AS, Sulzenbacher G, Canard B, Coutard B. Sci Rep 10 14422 PMID:32879358
Synthesis of Adenine Dinucleosides SAM Analogs as Specific Inhibitors of SARS-CoV nsp14 RNA Cap guanine-N7-methyltransferase (2020) Ahmed-Belkacem R, Sutto-Ortiz P, Guiraud M, Canard B, Vasseur JJ, Decroly E, Debart F.. Eur J Med Chem Jun 12;201 112557 PMID:0
Retrouver les origines du SARS-COV-2 dans les phylogenies de coronavirus (2020) Sallard E, Halloy H, Casane D, van Helden J., Decroly E. Med Sci (Paris) 36 783-796 PMID:32773024
Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase. (2020) Shannon A, Selisko B, Le N, Huchting J, Touret F, Piorkowski G, Fattorini V, Ferron F, Decroly E, Meier C, Coutard B, Peersen O, Canard B. bioRxiv May 15 PMID:32511380
Drugs against SARS-CoV-2: what do we know about their mode of action? (2020) Valle C, Martin B, Touret F, Shannon A, Canard B., Guillemot JC, Coutard B Decroly E.. Rev Med Virol in press PMID:32779326
In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication (2020) Touret F, Gilles M, Barral K, Nougairede A, van Helden J, Decroly E, de Lamballerie X, Coutard B. Sci Rep 10 13093 PMID:32753646

...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.