Institut Pasteur

Université Paris-Saclay

Centre National De La Recherche Scientifique

Oxford University Innovation Limited

Les Laboratoires Servier

Institut National De La Recherche Agronomique

Imperial College Innovations Limited

Université Paris—sud

Imperial College of Science, Technology and Medicine

Institut National De Recherche Pour L'agriculture, L'alimentation Et L'environnement

Stéphane Duquerroy

Felix Augusto Rey

Juthathip Mongkolsapaya

Marie-Christine Vaney

Alexander Rouvinski

Giovanna Barba-Spaeth

Pablo Guardado-Calvo

Patrick Couvreur

Didier Desmaele

Fabrice Agou

Michel Veron

Jean-François Eleouet

Gavin Screaton

Anny Slama Schwok

Bogdan Tarus

Screaton Gavin

Florence Cordier

Monika Dorota Kaminska

Olivera Grubisha

Elisabeth Fontan

Jeanne Chiaravalli

Christina Sizun

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or nonconsecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

Anti-dengue vaccines and antibodies

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or non-consecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

The present invention relates to N1-benzyl substituted pyrazoles as antiviral agents directed against respiratory syncytial virus.

Antiviral agents directed against respiratory syncytial virus

The invention relates to a crystal of the CC2-LZ domain of the NEMO protein, in which the three-dimensional structure has been determined by X-ray diffraction at a resolution of about 3.25 A. The invention also relates to methods for the crystallization of the CC2-LZ domain. The CC2-LZ crystals and the information derived from the crystalline structures thereof are used for identifying and designing compounds interacting with CC2-LZ.

Crystal structure of the CCZ-LZ domain of NEMO

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Paris, France

Stéphane Duquerroy