Influenza cap-leader sequence

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/11 (2006.01)

Patent

CA 2725289

The invention comprises a viral cap-leader sequence which comprises at least three bases complementary to the 3'--ultimate residues of a (-)ssRNA virus template sequence. Preferably said consensus sequence is represented by the general formula 7m G (N)6-10-(A/U/G)-A/U-AGC, more preferably 7m G (N)7-8- (A/U/G)-A/U-AGC. Further comprised are modified cap-leader se-quences that are able to block elongation by the viral polymerase or cleavage by the viral endonuclase. Such modified cap-leader sequences comprise a 3'-terminal phosphate group, one or more phosphorothioate or phosphorodiamidate bonds or one ore more morpholino rings. Also pharmaceutical products comprising such a modified cap- leader sequence are disclosed. Further, the in-vention comprises methods for inhibiting virus transcription, especially for influenza virus, using such a modified cap-leader se-quence or pharmaceutical product.

La présente invention concerne une séquence de tête-coiffe virale comprenant au moins trois bases complémentaires des ultimes résidus en 3' d'une séquence matrice d'un ARNss(-) viral. Ladite séquence consensus est, de préférence, représentée par la formule générale 7mG(N)6-10-(A/U/G)-A/U-AGC et, de façon encore préférée, par la formule 7mG(N)7-8-(A/U/G)-A/U-AGC. L'invention concerne, en outre, des séquences de tête-coiffe modifiées capables de bloquer l'élongation par la polymérase virale ou le clivage par l'endonucléase virale. Lesdites séquences de tête-coiffe modifiées comprennent un groupe phosphate 3'-terminal, une ou plusieurs liaisons phosphorothioate ou phosphorodiamidate ou un ou plusieurs cycles morpholino. L'invention concerne également des produits pharmaceutiques comprenant une telle séquence de tête-coiffe modifiée. En outre, l'invention concerne des procédés d'inhibition de la transcription virale, en particulier concernant le virus de la grippe, au moyen de ladite séquence de tête-coiffe modifiée ou dudit produit pharmaceutique.

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