European Molecular Biology Laboratory

F. Hoffmann-la Roche Ag

Savira Pharmaceuticals Gmbh

Other

Centre National De La Recherche Scientifique

Université Grenoble Alpes

University Joseph Fourier Filiale

Centre National De La Recherche Scientifique Direction De La Politique Industrielle

Stephen Cusack

Helmut Heinrich Buschmann

Norbert Handler

Oliver Szolar

Andrea Wolkerstorfer

Sung-Sau So

Mark Smith

Ronald Charles Hawley

Achyutharao Sidduri

Werner Neidhart

Tanja Schulz-Gasch

Robert James Weikert

Franz-Ferdinand Roch

Eva Kowalinski

Chloe Zubieta

Majid Mehtali

Zhuming Zhang

Bruno Giethlen

Christophe Morice

Darren James Hart

Franck Tarendeau

Val&eacute;rie Legrand

Denis Bouvier

Thibaut Crepin

Thibault Sauvaitre

Rob Ruigrok

Céline Simon

Aelxander Dias

Thierry Langer

Dirk Classen-Houben

Delphine Gulligay

Mark Johan Van Raaij

Philippe Leissner

Delphine Guilligay

Alexander Dias

Céline Michaut-simon

Laurence Jung

Céline Michaut-Simon

Thibault SAUVAÎTRE

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

Polypeptide fragments comprising endonuclease activity and their use

The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Cap/endo dual inhibitors and their use in the treatment, amelioration or prevention of a viral disease

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein the PA subunit is from Influenza A 2009 pandemic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of the polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of the polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods of identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit the endonucleolytic activity, as well as the compounds themselves. Preferably, the compounds are identifiable by the methods disclosed herein or the pharmaceutical compositions are producible by the methods disclosed herein.

Influenza A 2009 pandemic H1N1 polypeptide fragments comprising endonuclease activity and their use

The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameliorating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Substituted 1,5-naphthyridines as endonuclease inhibitors

The present invention relates to a compound having the general formula (A), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

7-oxo-thiazolopyridine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease

Substituted naphthyridines for the treatment, amelioration or prevention of a viral disease

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein said PA subunit is from Influenza A 2009 pandemic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds which are able to modulate, preferably to inhibit, the endonuclease activity of the PA subunit polypeptide fragment or variant thereof of the present invention and pharmaceutical compositions comprising said compounds for the treatment of disease conditions caused by viral infections with viruses of the Orthomyxoviridae family, Bunyaviridae family and/or Arenviridae family, preferably caused by viral infections with Influenza A 2009 pandemic H1N1 virus. Preferably, said compounds are identifiable by the methods disclosed herein or said pharmaceutical compositions are producible by the methods disclosed herein.

The present invention relates to a compound having the general formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Pyrimidone derivatives and their use in the treatment, amelioration or prevention of a viral disease

The present invention relates to soluble fragments of the Influenza virus RNA dependent RNA polymerase subunit PB2 and variants thereof, and crystallized complexes thereof comprising an RNA cap analog. This invention also relates to computational methods using the structural coordinates of said complex to screen for and design compounds that interact with the RNA cap binding pocket. In addition, this invention relates to methods identifying compounds that bind to PB2 polypeptide fragments comprising the RNA cap binding pocket, preferably inhibit the interaction with RNA caps or analogs thereof, by using said PB2 polypeptide fragments, preferably in a high-throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by negative-sense single stranded RNA viruses.

Soluble fragments of influenza virus PB2 protein capable of binding RNA-cap

The present invention relates to a compound having the general formula (II), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Pyridone derivatives and their use in the treatment, ameloriation or prevention of a viral disease

The present invention relates to a compound having the general formula (Di), (Dii), or (Diii), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Dihydroxypyrimidine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease

The present invention relates to a modified fiber of an adenovirus, comprising at least one mutation at one or more residues within the region of said fiber stretching from pleated sheet A to pleated sheet B, and including loop AB.

Modified adenoviral fibre and uses thereof

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Seyssinet-Pariset, France

Stephen Cusack