Antisense antiviral compound and method for treating ss/RNA viral infection
The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornaviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.
1. A morpholino subunit of formula:
or a salt or isomer thereof, wherein:
B is a base-pairing moiety;
R i is C 1 -C 12 alkylcarbonyl;
R 2 is C 7 -C 30 aralkyl; and
Z is halo.
2. The morpholino subunit of claim 1 , wherein R i is trifluoroacetyl.
3. The morpholino subunit of claim 1 , wherein R 2 is trityl.
4. The morpholino subunit of claim 1 , wherein R 2 is 4-methoxytrityl.
5. The morpholino subunit of claim 1 , wherein Z is chloro.
6. The morpholino subunit of claim 1 , wherein B is adenine, cytosine, guanine, uracil, thymine, or hypoxanthine.
7. The morpholino subunit of claim 1 , wherein B comprises one or more protecting groups.
8. The morpholino subunit of claim 1 , wherein B is adenine, cytosine, guanine, uracil, thymine or hypoxanthine, each of which comprise at least one protecting group.
9. The morpholino subunit of claim 1 , wherein the morpholino subunit is of formula:
or a salt or isomer thereof, wherein B is a base-pairing moiety.