Head of the “Medicinal Antiviral Chemistry” thematic group

Diplomas

  • 2006, HDR (Discipline: Chemical Sciences), Univ Aix-Marseille II. Title: “Contribution to the discovery and development of active compounds against viral polymerases”.
  • 1999, PhD in Organic, Mineral and Industrial Chemistry, Univ Montpellier II. Dir Dr J.J. Vasseur, laboratory of Bio-Organic Chemistry. Title : “Prodrogues of oligonucleotides : research of new nucleobase protective groups adapted to the automated synthesis of prooligonucleotides”.
  • 1995 D.E.A in Chemistry of Biomolecules, Univ Montpellier II

Professional experiences

  • Since 2019, DR2 CNRS, INC section 16, AFMB, CNRS-UMR 7257
  • Since 10/2001, CR2 then CR1 CNRS, INC section 16, Laboratory of Architecture and Function of Biological Macromolecules (AFMB), CNRS-UMR 7257
    Project 1 : Finding new nucleotide analogues to circumvent the resistance of HIV RT to nucleoside drugs.
    Project 2: Hepatitis C virus NS5B polymerase as an antiviral target
    Project 3: Bunyavirales nucleases as targets of future therapies: development of screening tools and search for antivirals.
    Project 4: The L protein of the Arenaviridae for a drug design strategy
    Project 5: Contribution to the development of antivirals against SARS-Cov-2 infections
  • From 06/2000 to 09/2001, Post-Doctoral internship, Faculty of Physics-Chemistry of Barcelona. Laboratory of Pr E. PEDROSO. EU grant. Subject : “Anthracene conjugates as probes of telomere structure and function”. Development of new telomerase inhibitors based on the association of anthracene derivatives with oligonucleotide and/or peptide macromolecules.

Publications

2022

2022
Arenaviridae NP-exonuclease inhibition by bisphosphonate

Thi Hong van Nguyen, Elsie yekwa, Barbara Selisko, Bruno Canard, Karine Alvarez, Francois Ferron

IUCrJ 9 (2022)10.1107/S2052252522005061

2022
A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Ashleigh Shannon, Véronique Fattorini, Bhawna Sama, Barbara Selisko, Mikael Feracci, Camille Falcou, Pierre Gauffre, Priscila El Kazzi, Adrien Delpal, Etienne Decroly, Karine Alvarez, Cécilia Eydoux, Jean-Claude Guillemot, Adel Moussa, Steven S Good, Paolo La Colla, Kai Lin, Jean-Pierre Sommadossi, yingxiao Zhu, Xiaodong yan, Hui Shi, Francois Ferron, Bruno Canard

Nature Communications 13 (2022)10.1038/s41467-022-28113-1

2021

2021
Observation of arenavirus nucleoprotein heptamer assembly

Nicolas Papageorgiou, Afroditi Vaitsopoulou, Awa Diop, Thi Hong van Nguyen, Bruno Canard, Karine Alvarez, Francois Ferron

FEBS Open Bio (2021)10.1002/2211-5463.13106

2020

2020
Brothers in Arms: Structure, Assembly and Function of Arenaviridae Nucleoprotein

Nicolas Papageorgiou, Maria Spiliopoulou, Thi-Hong van Nguyen, Afroditi Vaitsopoulou, Elsie yekwa Laban, Karine Alvarez, Irene Margiolaki, Bruno Canard, Francois Ferron

Viruses 12:772 (2020)10.3390/v12070772

2020
Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites

Ashleigh Shannon, Nhung Thi-Tuyet Le, Barbara Selisko, Cecilia Eydoux, Karine Alvarez, Jean-Claude Guillemot, Etienne Decroly, Olve Peersen, Francois Ferron, Bruno Canard

Antiviral Research 178:104793 (2020)10.1016/j.antiviral.2020.104793

2020
Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1 H -pyrazole-5-carboxylate as an HIV-1 replication inhibitor

Jeanne Fichez, Cathia Soulié, Laurent Le Corre, Sophie Sayon, Stéphane Priet, Karine Alvarez, Olivier Delelis, Patrick Gizzi, Guillaume Prestat, Christine Gravier-Pelletier, Anne-Geneviève Marcelin, Vincent Calvez, Patricia Busca

RSC Medicinal Chemistry 11:577-582 (2020)10.1039/D0MD00025F

2019

2019
Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues.

Antoine Frangeul, Cécile Bussetta, Jérôme Deval, Karine Barral, Karine Alvarez, Bruno Canard

Antiviral Therapy 13:115-24 (2019)

2019
Metal chelators for the inhibition of the lymphocytic choriomeningitis virus endonuclease domain

Magali Saez-Ayala, Elsie Laban yekwa, Clémence Mondielli, Loic Roux, Sergio Hernández, Fabrice Bailly, Philippe Cotelle, Dominga Rogolino, Bruno Canard, Francois Ferron, Karine Alvarez

Antiviral Research 162:79-89 (2019)10.1016/j.antiviral.2018.12.008

2019
Identification of a new natural gastric lipase inhibitor from star anise

Jannet Kamoun, Renaud Rahier, Mohamed Sellami, Imed Koubaa, Pascal Mansuelle, Régine Lebrun, Alexandra Berlioz-Barbier, Michele Fiore, Karine Alvarez, Abdelkarim Abousalham, Frédéric Carrière, Ahmed Aloulou

Food and Function 10:469-478 (2019)10.1039/c8fo02009d

2018

2018
Crystal structures of Lymphocytic choriomeningitis virus endonuclease domain complexed with diketo-acid ligands

Magali Saez-Ayala, Elsie Laban yekwa, Mauro Carcelli, Bruno Canard, Karine Alvarez, Francois Ferron

International Union of Crystallography journal 5:223-235 (2018)10.1107/S2052252518001021

2018
Crystal structures ofLymphocytic choriomeningitis virusendonuclease domain complexed with diketo-acid ligands

Magali Saez-Ayala, Elsie yekwa, Mauro Carcelli, Bruno Canard, Karine Alvarez, Francois Ferron

International Union of Crystallography journal 5:223-235 (2018)10.1107/s2052252518001021

2018
Synthesis and substrate properties towards HIV-1 reverse transcriptase of new diphosphate analogues of 9-[(2-phosphonomethoxy)ethyl]adenine

Wolfgang Hg Laux, Stephane Priet, Karine Alvarez, Suzanne Peyrottes, Christian Perigaud

Antiviral Chemistry and Chemotherapy 26:204020661875763 (2018)10.1177/2040206618757636

2018
How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

Amandine Pasquier, Sandrine Alais, Loic Roux, Maria-Isabel Thoulouze, Karine Alvarez, Chloé Journo, Hélène Dutartre, Renaud Mahieux

Frontiers in Microbiology 9:278 (2018)10.3389/fmicb.2018.00278

2017

2017
Contribution to PNA-RNA Chimera Synthesis: One-Pot Microwave-Assisted Ugi Reaction to Obtain Dimeric Building Blocks

Reuben Ovadia, Clémence Mondielli, Jean-Jacques Vasseur, Carine Baraguey, Karine Alvarez

European Journal of Organic Chemistry 2017:469-475 (2017)10.1002/ejoc.201601190

2016

2016
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

Fatiha Benmansour, Cecilia Eydoux, Gilles Querat, Xavier de Lamballerie, Bruno Canard, Karine Alvarez, Jean-Claude Guillemot, Karine Barral

European Journal of Medicinal Chemistry 109:146-156 (2016)10.1016/j.ejmech.2015.12.046

2015

2015
Synthesis and structural characterization of monomeric and dimeric peptide nucleic acids prepared by using microwave-promoted multicomponent reactions

Reuben Ovadia, Aurelien Lebrun, Ivan Barvik, Jean-Jacques Vasseur, Carine Baraguey, Karine Alvarez

Organic and Biomolecular Chemistry 13:11052-11071 (2015)10.1039/c5ob01604e

2015
Enzymatic synthesis of acyclic nucleoside thiophosphonate diphosphates: Effect of the alpha-phosphorus configuration on HIV-1 RT activity

Stephane Priet, Loic Roux, Magali Saez-Ayala, Francois Ferron, Bruno Canard, Karine Alvarez

Antiviral Research 117:122-131 (2015)10.1016/j.antiviral.2015.03.003

2011

2011
Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication

Karine Barral, Clément Weck, Nadine Payrot, Loic Roux, Céline Durafour, Fabien Zoulim, Johan Neyts, Jan Balzarini, Bruno Canard, Stephane Priet, Karine Alvarez

European Journal of Medicinal Chemistry 46:4281-4288 (2011)10.1016/j.ejmech.2011.06.034

2010

2010
Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates

Karine Barral, Stephane Priet, Céline de Michelis, Joséphine Sire, Johan Neyts, Jan Balzarini, Bruno Canard, Karine Alvarez

European Journal of Medicinal Chemistry 45:849-856 (2010)10.1016/j.ejmech.2009.11.012

2010
3'-Deoxy phosphoramidate dinucleosides as improved inhibitors of Hepatitis C virus subgenomic replicon and NS5B polymerase activity.

Stephane Priet, Ivan Zlatev, Ivan Barvik, Katrien Geerts, Pieter Leyssen, Johan Neyts, Hélène Dutartre, Bruno Canard, Jean-Jacques Vasseur, François Morvan, Karine Alvarez

Journal of Medicinal Chemistry 53:6608-6617 (2010)10.1021/jm100102v

2009

2009
Identification of allosteric inhibitors blocking the hepatitis C virus polymerase NS5B in the RNA synthesis initiation step.

Stéphane Betzi, Cécilia Eydoux, Cécile Bussetta, Marilyne Blemont, Pieter Leyssen, Claire Debarnot, Mohamed Ben-Rahou, Jacques Haiech, Marcel Hibert, Françoise Gueritte, David S. Grierson, Jean-Louis Romette, Jean-Claude Guillemot, Johan Neyts, Karine Alvarez, Xavier Morelli, Hélène Dutartre, Bruno Canard

Antiviral Research 84:48-59 (2009)10.1016/j.antiviral.2009.06.009

2006

2006
Synthesis, in Vitro Antiviral Evaluation, and Stability Studies of Novel α-Borano-Nucleotide Analogues of 9-[2-(Phosphonomethoxy)ethyl]adenine and ( R )-9-[2-(Phosphonomethoxy)propyl]adenine

Karine Barral, Stephane Priet, Joséphine Sire, Johan Neyts, Jan Balzarini, Bruno Canard, Karine Alvarez

Journal of Medicinal Chemistry 49:7799-7806 (2006)10.1021/jm060030y

2005

2005
Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance

Karine Alvarez, Jérôme Deval, Boulbaba Selmi, Karine Barral, Joelle Boretto, Catherine Guerreiro, Laurence S Mulard, Robert Sarfati, Bruno Canard

Nucleosides, Nucleotides and Nucleic Acids 24:419-422 (2005)10.1081/NCN-200059951

2004

2004
Crystal Structure of E. coli Alcohol Dehydrogenase YqhD: Evidence of a Covalently Modified NADP Coenzyme

Gerlind Sulzenbacher, Karine Alvarez, Robert H H van den Heuvel, Cees Versluis, Silvia Spinelli, Valé Rie Campanacci, Christel Valencia, Christian Cambillau, Hans Eklund, Mariella Tegoni

Journal of Molecular Biology 342:489-502 (2004)10.1016/j.jmb.2004.07.034

1998

1998
The pro-oligonucleotide approach: solid phase synthesis and preliminary evaluation of model pro-dodecathymidylates

J.J. Vasseur, Guilhem Tosquellas, Karine Alvarez, Christelle Dell'Aquila, François Morvan, Jean-Jacques Vasseur, Jean-Louis Imbach, Bernard Rayner

Nucleic Acids Research 26:2069-2074 (1998)10.1093/nar/26.9.2069