Viral Replicases: Structure, function and drug-design

Head Bruno CANARD

Latest Publications

[Innate immunity evasion mechanisms of filoviruses]. (2018) Martin B, Decroly E. Med Sci (Paris) 34 671-677 PMID:30230452
Crystal structures of Lymphocytic choriomeningitis virus endonuclease domain complexed with diketo-acid ligands. (2018) Saez-Ayala M, Yekwa EL, Carcelli M, Canard B, Alvarez K, Ferron F. IUCrJ 5 223-235 PMID:29765612
Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases. (2018) Selisko B, Papageorgiou N, Ferron F, Canard B. Viruses 10 PMID:29385764
How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy. (2018) Pasquier A, Alais S, Roux L, Thoulouze MI, Alvarez K, Journo C, Dutartre H, Mahieux R. Front Microbiol 9 278 PMID:29593659
Synthesis and substrate properties towards HIV-1 reverse transcriptase of new diphosphate analogues of 9-[(2-phosphonomethoxy)ethyl]adenine. (2018) Laux WH, Priet S, Alvarez K, Peyrottes S, Perigaud C. Antivir Chem Chemother 26 2040206618757636 PMID:29436843
The European Virus Archive goes global: A growing resource for research. (2018) Romette JL, Prat CM, Gould EA, de Lamballerie X, Charrel R, Coutard B, Fooks AR, Bardsley M, Carroll M, Drosten C, Drexler JF, Gunther S, Klempa B, Pinschewer D, Klimkait T, Avsic-Zupanc T, Capobianchi MR, Dicaro A, Ippolito G, Nitsche A, Koopmans M, Reusken C, Gorbalenya A, Raoul H, Bourhy H, Mettenleiter T, Reiche S, Batten C, Sabeta C, Paweska JT, Eropkin M, Zverev V, Hu Z, Mac Cullough S, Mirazimi A, Pradel F, Lieutaud P. Antiviral Res 158 127-134 PMID:30059721

...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.