Novel anti-viral therapeutic
AssigneeThe Regents of the University of California
InventorsBert L. Semler, Richard Virgen-Slane, Janet M. Rozovics, Paul D. Gershon
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Abstract
Anti-viral therapeutics for use in viral targets having VPg unlinkase activity, including the broad class of picornaviruses, and therapeutic methods directed at suppression of such activity are provided. Such anti-viral therapies for use against human rhinovirus, for example, are particularly desirable as they would lessen both the severity and duration of upper respiratory distress in both normal and asthmatic individuals. Assays and purification protocols for detecting and purifying VPg unlinkase are also provided.
Claims20
A method of treatment or inhibiting picornavirus replication, said method comprising:
- administering a therapeutically effective amount of an inhibitor compound to a human host infected with a picornavirus, said step of administering comprising one of intranasal, oral or intravenous administration of the inhibitor compound to the human host;
- and
- wherein the inhibitor compound inhibits the release of picornavirus viral protein genome-linked (VPg) by tyrosyl-DNA phosphodiesterase 2 (TDP2).
A method of treatment or inhibiting picornavirus replication, said method comprising:
- administering a therapeutically effective amount of a synthetic nucleic acid polymer inhibitor to a human host infected with a picornavirus, said step of administering comprising one of intranasal, oral or intravenous administration of the inhibitor;
- wherein the synthetic nucleic acid compound is selected from the group consisting of a single-stranded deoxyribonucleic acid (ssDNA) polymer and a single-stranded ribonucleic acid (ssRNA) polymer;
- and
- wherein the inhibitor inhibits the release of picornavirus VPg by tyrosyl-DNA phosphodiesterase 2 (TDP2).
An assay for monitoring the release of viral protein, genome-linked (VPg) from picornavirus genomic RNA generally comprising:
- generating a picornavirus genomic RNA containing an 35S-labeled VPg;
- incubating the 35S-labeled VPg with an extraction comprising tyrosyl-DNA phosphodiesterase 2 (TDP2);
- running the 35S-labeled VPg in a gel electrophoresis apparatus;
- and
- monitoring the cleavage of the labeled VPg from the picornavirus genomic RNA.
A tyrosyl-DNA phosphodiesterase 2 (TDP2) purification protocol comprising:
- providing a cell homogenate that contains TDP2;
- and
- sequentially fractionating the supernatant by heparin Sepharose, ssDNA-cellulose, anion exchange, size exclusion, and cation exchange chromatography to produce a substantially homogeneous enzyme preparation.
Dependencies are inferred from the claim text.