Antisense antiviral compound and method for treating ssRNA viral infection

摘要

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornoviridae, 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.

主权项

1. A method of inhibiting replication of a Coronavirus in a mammalian host cell, comprising
administering to the infected mammalian host cells, a virus-inhibitory amount of an oligonucleotide analog coumpound characterized by: (i) a nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 12-40 nucleotide bases, and (iv) having a targeting sequence of at least 12 subunits 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 Coronavirus, and by said administering, forming within the infected mammalian host cell, a heteroduplex structure (i) composed of the positive-sense RNA strand of the Coronavirus and the oligonucleotide analog compound, and (ii) characterized by a Tm of dissociation of at least 45° C. and disruption of a stem-loop secondary structure.