- Enzymatic synthesis of acyclic nucleoside thiophosphonate diphosphates: effect of the alpha-phosphorus configuration on HIV-1 RT activity. (2015) Priet S, Roux L, Saez-Ayala M, Ferron F, Canard B, Alvarez K. Antiviral Res 117 122-31 PMID:25766862
- Ester prodrugs of acyclic nucleoside thiophosphonates compared to phosphonates: Synthesis, antiviral activity and decomposition study. (2013) Roux L, Priet S, Payrot N, Weck C, Fournier M, Zoulim F, Balzarini J, Canard B, Alvarez K. Eur J Med Chem 63C 869-881 PMID:23603046
- 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 PMID:20799693
- 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 PMID:18611413
The team’s objective is to design and synthesize antiviral molecules targetting human pathogenic viruses (HIV, HCV, SRAS, LCMV, Dengue...) for which there is no treatment and to design more potent antiviral molecules than those currently used in therapy.
In antiviral research, two drug-discovery strategies are used: one based on the rational design of molecules helped with biochemistry and structural biology and the other based on the HTS synthesis of molecules identified by screening, in a process of hit-to-lead optimisation. In both approaches, the targets are enzymes belonging to the viruses replicative complex. The originality and quality of work being done are due to the multidisciplinary of the projects combining structural biology, crystallography, enzymology, biochemistry and chemistry. Four themes are developped :
- Design of new nucleotide analogues to circumvent the resistance of HIV RT to nucleo(si)tides.
- Development of chemotherapy against Flaviviruses.
- The NS5B polymerase of HCV as antiviral target.
- Rational design of molecules to inhibit the L protein of Arenaviridae.