CNRS - AIX MARSEILLE UNIV: UMR7257

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Antiviral Medicinal Chemistry

Head Karine ALVAREZ

Latest Publications

  1. 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
  2. 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
  3. 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
  4. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase. (2016) Benmansour F, Eydoux C, Querat G, de Lamballerie X, Canard B, Alvarez K, Guillemot JC, Barral K. Eur J Med Chem 109 146-56 PMID:26774922
  5. Synthesis and structural characterization of monomeric and dimeric peptide nucleic acids prepared by using microwave-promoted multicomponent reactions. (2015) Ovadia R, Lebrun A, Barvik I, Vasseur JJ, Baraguey C, Alvarez K. Org Biomol Chem 13 11052-71 PMID:26394794
  6. 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
...All publications

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.

Drug-discovery

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 :

  1. Design of new nucleotide analogues to circumvent the resistance of HIV RT to nucleo(si)tides.
  2. Development of chemotherapy against Flaviviruses.
  3. The NS5B polymerase of HCV as antiviral target.
  4. Rational design of molecules to inhibit the L protein of Arenaviridae.

Karine ALVAREZ
Sergio HERNANDEZ
Rafik KACI
Clémence MONDIELLI

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