The study of polymerases is one of the most important research topics in the laboratory (HIV, HCV, dengue West Nile SARS CoV, BVDV, Coxsackie virus). We have developed many tools to monitor their enzymatic activity. Our work allowed recently to solve the 3D structure of several polymerases, to contribute to the characterization of their complex enzymatic mechanism, and to identify active partners in multi-protein complexes. We have also developed original inhibitors and studied the mechanisms governing the resistance against these antivirals.
- Structure of West Nile virus polymerase
Some references
Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication. (2011)
Barral K, Weck C, Payrot N, Roux L, Durafour C, Zoulim F, Neyts J, Balzarini J, Canard B, Priet S, Alvarez K
Eur J Med Chem 46 : 4281-8
3'-Deoxy phosphoramidate dinucleosides as improved inhibitors of hepatitis C virus subgenomic replicon and NS5B polymerase activity. (2010)
Priet S, Zlatev I, Barvik I, Geerts K, Leyssen P, Neyts J, Dutartre H, Canard B, Vasseur JJ, Morvan F, Alvarez K
J Med Chem 53 : 6608-17
RNA-dependent RNA polymerases from flaviviruses and Picornaviridae. (2009)
Lescar J, Canard B
Curr Opin Struct Biol 19 : 759-767
Identification of allosteric inhibitors blocking the Hepatitis C Virus polymerase NS5B in the RNA synthesis initiation step. (2009)
Betzi S, Eydoux C, Bussetta C, Blemont M, Leyssen P, Debarnot C, Ben-Rahou M, Haiech J, Hibert M, Gueritte F, Grierson DS, Romette JL, Guillemot JC, Neyts J, Alvarez K, Morelli X, Dutartre H, Canard B
Antiviral Res 84 : 48-59
The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases. (2008)
Gruez A, Selisko B, Roberts M, Bricogne G, Bussetta C, Jabafi I, Coutard B, De Palma AM, Neyts J, Canard B
J Virol 82 : 9577-90
The flavivirus polymerase as a target for drug discovery. (2008)
Malet H, Masse N, Selisko B, Romette JL, Alvarez K, Guillemot JC, Tolou H, Yap TL, Vasudevan S, Lescar J, Canard B
Antiviral Res 80 : 23-35
A second, non-canonical RNA-dependent RNA polymerase in SARS Coronavirus (2006)
Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B
EMBO J 25 : 4933-4942
Comparative mechanistic studies of de novo RNA synthesis by flavivirus RNA-dependent RNA polymerases. (2006)
Selisko B, Dutartre H, Guillemot JC, Debarnot C, Benarroch D, Khromykh A, Despres P, Egloff MP, Canard B
Virology 351 : 145-58
