# US 2010/0166704 A1 · Methods and compositions for inhibition of viral replication

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- Number: US 2010/0166704 A1
- Document ID: US20100166704A1
- Status: Published application
- Kind: A1
- Application number: 12/082,095
- Filed: 2008-04-07
- Published: 2010-07-01
- Earliest claimed: 2002-08-30
- Inventors: Margo A. Brinton; Mohamed M. Emara; Wei Li
- Web page: https://patentgrep.com/patent/US20100166704A1

## CPC

- A61K 38/162: {from virus}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/1131: {against viruses}
- C12N 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- C12Q 1/18: Testing for antimicrobial activity of a material
- C12N 2310/13: Decoys
- C12N 2770/24111: Flavivirus, e.g. yellow fever virus, dengue, JEV
- G01N 2333/18: Togaviridae; Flaviviridae
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention is directed to methods and compositions that are effective in the inhibition of viral replication. In particular, the methods and compositions are effective at interfering with the activity of host cell proteins required in viral replication. For example, an embodiment of the invention is directed to inhibition of flavivirus replication wherein the replication is affected by changing the normal interactions of the host cell protein TIAR or TIA-1.

## Claims

### Claim 1

A method of inhibiting replication of a flavivirus, comprising,
administering an effective amount of a composition; and
inhibiting flavivirus replication by inhibiting or interfering with at least one host cell protein associated with replication of a flavivirus

### Claim 2 (depends on 1)

The method of claim 1, wherein the flavivirus is West Nile virus.

### Claim 3 (depends on 1)

The method of claim 1, wherein the flavivirus is Dengue virus.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition comprises a nucleic acid construct of the 3′ end of the negative strand nucleic acid of a flavivirus or a nucleic acid construct that mimics the 3′ end of the negative strand nucleic acid of a flavivirus.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition comprises a peptide that mimics a region of at least one viral protein that interacts with at least one host cell protein.

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition comprises a compound that interferes with at least one host cell protein associated with replication of a flavivirus.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least one host cell protein is TIAR, TIA-1, p50, p60, p108, p52, p84, or p105.

### Claim 8

A method of inhibiting replication of a flavivirus, comprising,
administering an effective amount of a composition; and
inhibiting flavivirus replication by inhibiting or interfering with the interaction or association of at least one host cell protein and at least one viral protein.

### Claim 9 (depends on 8)

The method of claim 8, wherein the flavivirus is West Nile virus.

### Claim 10 (depends on 8)

The method of claim 8, wherein the composition comprises a protein, polypeptide, peptide, or amino acid sequence that mimics a region of the at least one viral protein that interacts with at least one host cell protein.

### Claim 11 (depends on 9)

The method of claim 9, wherein the at least one viral protein is the capsid protein, membrane protein, envelope protein, NS1, NS2a, NS2b, NS3, NS4a, NS4b, or NS5 of West Nile virus.

### Claim 12 (depends on 8)

The method of claim 8, wherein the flavivirus is Dengue virus.

### Claim 13 (depends on 8)

The method of claim 8, wherein the at least one viral protein is a structural or non-structural protein of Dengue virus.

### Claim 14 (depends on 8)

The method of claim 8, wherein the at least one host cell protein is TIA-1, TIAR p50, p60, p108, p52, p84, or p105.

### Claim 15

A method of inhibiting replication of a flavivirus, comprising,
administering an effective amount of a composition; and
inhibiting flavivirus replication by inhibiting or interfering with a host cell signaling pathway.

### Claim 16 (depends on 15)

The method of claim 15, wherein the composition comprises double-stranded RNA, interferons, viruses, replication-deficient viruses, small molecules, small organic molecules, cytokines, chemokines, viral vectors, proteins, peptides, peptide agonists, growth factors, nucleic acid, antibodies, peptoids, polyanions, or other cell signaling proteins or molecules.

### Claim 17 (depends on 15)

The method of claim 15, wherein the host cell signaling pathway comprises eIF2α or PKR