Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA
AssigneeUniversity of Washington
InventorsLawrence A. Loeb, James I. Mullins
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Abstract
The present invention is directed to the identification and use of ribonucleoside analogs to induce the mutation of an RNA virus, including BVDV, HIV and HCV, or a virus which otherwise replicates through an RNA intermediate. The increase in the mutation rate of the virus results in reduced viability of progeny generations of the virus, thereby inhibiting viral replication. In addition to these methods and related compositions, the invention provides methods and combinatorial chemistry libraries for screening ribonucleoside analogs for mutagenic potential.
Claims24
A method of increasing the mutation rate of a retrovirus or flavivirus, comprising administering an RNA nucleoside analog to a virally infected cell, wherein the analog is incorporated by a polymerase into an RNA copy of a genomic nucleic acid encoding the retrovirus or flavivirus, said analog replacing a first natural occurring nucleotide having a first complementary nucleotide wherein said analog complements a second nucleotide which is other than the first nucleotide, thereby inducing the retrovirus or flavivirus to mutate.
A method of increasing the mutation rate of a virus, comprising administering an RNA nucleoside analog to a virally infected cell, wherein the analog is incorporated by a polymerase into an RNA copy of a genomic nucleic acid encoding the virus, said analog replacing a first natural occurring nucleotide having a first complementary nucleotide wherein said analog complements a second nucleotide which is other than the first nucleotide, thereby inducing the virus to mutate, wherein the virus is an RNA virus selected from the group consisting of hepatitis C, coronavirus, influenza, respiratory syncytial virus, BVDV, and dengue fever.
A method of increasing the mutation rate of a virus in an animal comprising administering to the animal a therapeutically effective dose of a mutagenic ribonucleoside analog composition wherein the analog is one that, in a cell infected with a virus of interest, is incorporated by a polymerase into an RNA copy of a genomic nucleic acid encoding the virus, said analog replacing a first natural occurring nucleotide having a first complementary nucleotide wherein said analog complements a second nucleotide which is other than the first nucleotide together with a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.