Screening of antiviral compounds targeted to the hiv-1 gp41...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/70 (2006.01) A61K 31/53 (2006.01) A61K 39/21 (2006.01) A61K 39/395 (2006.01) C07K 16/00 (2006.01) C07K 16/10 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2362532

A method for the screening of antiviral compounds targeted to the HIV- 1 gp41 core structure comprising capturing polyclonal antibodies from an animal other than a mouse directed against a trimer of a heterodimer containing an N- peptide and a C- peptide onto a solid- phase, mixing a compound to be tested with an N- peptide and then adding a C- peptide, adding the resultant mixture to the resultant polyclonal antibody coated solid- phase and then removing unbound peptides and unbound compound, adding a monoclonal antibody directed against the trimer of a heterodimer containing an N- peptide and a C- peptide and measuring the antibody binding of the monoclonal antibody. A method for inhibiting HIV- 1 virus replication or infectivity in a patient by administering to the patient an antiviral compound targeted to the HIV- 1 gp41 core structure selected from the group consisting of 7- [6- phenylamino- 4[4- [(3,5- disulfo- 8- hydroxynaphthyl)azo]- 2- methoxy- 5- methyl- phenylamino]- 1,3,5- triazine- 2- yl]- 4- hydroxy- 3- [(2- methoxy- 5- sulfophenyl)azo]- 2- naphthalene sulfonic acid and 5- [(4- chloro- 6- phenylamino- 1,3,5- triazine- 2- yl)- aminol]- 4- hydroxy- 3- (4- methyl- 5- sulfophenyl)azo]- 2,7- naphthalene disulfonic acid.

L'invention concerne une méthode de criblage de composés antiviraux ciblant le noyau de la glycoprotéine gp41 du VIH-1, laquelle méthode consiste à piéger, sur une phase solide, des anticorps polyclonaux d'un animal autre que la souris dirigés contre un trimère d'hétérodimère contenant un peptide N et un peptide C ; à mélanger le composé à analyser avec un peptide N, puis à ajouter un peptide C ; à ajouter le mélange obtenu à la phase solide enrobée d'anticorps polyclonaux obtenue, puis à éliminer les peptides et les composés non fixés ; à ajouter un anticorps monoclonal dirigé contre le trimère d'un hétérodimère contenant un peptide N et un peptide C ; et à mesurer la liaison de l'anticorps monoclonal. L'invention concerne également une méthode destinée à inhiber la réplication ou l'infectiosité du virus VIH-1 chez un patient par l'administration d'un composé antiviral ciblant le noyau de la gp41 du VIH-1 sélectionné dans le groupe constitué de l'acide 7-[6-phénylamino-4[4-[(3,5-disulfo-8-hydroxynaphthyl)azo]-2-méthoxy-5-méthyl-phénylamino]-1,3,5-triazine-2-yl]-4-hydroxy-3-[(2-méthoxy-5-sulfophényl)azo]-2-naphthalène sulfonique et de l'acide 5-[(4-chloro-6-phénylamino-1,3,5-triazine-2-yl)-amino]-4-hydroxy-3-[(4-méthyl-5-sulfophényl)azo]-2,7-naphthalène disulfonique.

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