Method to block the infection by flaviviruses, molecules and uses

• US 8,420,311 B2
• Filed: 04/26/2007
• Issued: 04/16/2013
• Est. Priority Date: 04/28/2006
• Status: Active Grant

• Current Assignee: Centro De Ingenieria Genetica Y Biotecnologia
• Original Assignee: Centro De Ingenieria Genetica Y Biotecnologia
• Inventors: Santiago, Glay Chinea, Puente, Aniel Sanchez, Galindo, Vivian Huerta, Perez, Vladimir Armando Besada, Lopez, Luis Javier Gonzalez, Dunn, Alejandro Miguel Martin, Rico, Ania Cabrales, Nunez, Monica Sarria, Perez, Hilda Elisa Garay, Salazar, Noralvis Fleitas, Cruz, Osmany Guirola, Acosta, Osvaldo Reyes, Lasa, Alexis Musacchio, Mayora, Patricia Gabriela Toledo, Palomares, Gabriel Ramon Padron
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US12/298,808
• Publication Number:
  US 20110212105A1
• Time in Patent Office: 2,182 Days
• Field of Search: None
• US Class Current: 435/5
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/70596 Molecules with a "CD"-designation not provided for elsewhere
• CPC Class Codes: C07K 14/8107 Endopeptidase (E.C. 3.4.21-99) inhibitors
• CPC Class Codes: C12N 2770/24122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is related to a method for blocking the infection of cells by dengue virus, based on interfering the direct interaction of the viral envelope protein with a cellular receptor or its indirect interaction with said cellular receptor through a carrier protein, as well as related uses; wherein said cellular receptor is the alpha-2 macroglobulin receptor, also known as the low density receptor-related protein or as CD91, and said carrier protein is human alpha-2 macroglobulin.

Claims

1. A method for blocking the infection by flaviviruses, said method comprising interfering with the interaction of the viral envelope protein with the alpha-2 macroglobulin receptor identified in the sequence listing as SEQ ID NO:

3, wherein the agent that interferes with the interaction of the virus with the receptor is the peptide identified as SEQ ID NO;

7.

2. A method according to claim 1 wherein the flavivirus is the dengue virus, the Yellow Fever Virus, the Japanese Encephalitis virus, the Tick-Borne Encephalitis virus, the Murray Valley Encephalitis virus, the West Nile Virus, the Kunjin virus, the Powasan virus, the Langat virus or the Saint Louis Encephalitis virus.

3. A method according to claim 1 wherein the sequence of the viral protein is at least 60% homologous to the sequence identified in the sequence listing as SEQ ID NO:

1.

4. A method according to claim 1 wherein the agent that interferes with the interaction of the viral envelope protein with the protein identified in the sequence listing as SEQ ID NO:

3 is obtained by chemical synthesis, or by recombinant DNA techniques, or from a natural source.

5. A method according to claim 1 wherein said peptide is modified to include

an optional N-terminal extension formed by a chemical group covalently bonded to the N-terminal group cysteine;

and an optional C-terminal extension formed by a chemical group covalently bonded to the terminal carbonyl group of the C-terminal cysteine;

wherein the N-terminal cysteine and C-terminal cysteine form a disulphide bridge.

6. A method according to claim 1 wherein the agent that blocks the infection interferes with the interaction of the protein identified in the sequence listing as SEQ ID NO:

1 with one or more of the residues defined as a ligand binding patch of the protein identified in the sequence listing as SEQ ID NO;

3.

7. A method according to claim 1 wherein the agent interfering with the viral interaction is the active principle of a pharmaceutical composition.

8. The method according to claim 5, wherein the chemical group convalently bonded to the N-terminal or C-terminal cysteine is selected from the group consisting of an acetyl group, methyl group, acyl group, or polyethylene glycol.