Antisense antiviral compound and method for treating arenavirus infection

A method of inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, comprising

• (a) exposing the cells to an antisense oligonucleotide compound capable of uptake by mammalian host cells, wherein the antisense oligonucleotide compound is comprised of morpholino subunits and phosphorous-containing intersubunit linkages having the following structure (I):
• wherein:
• Y1=O;
• Z=O;
• Pi and Pj are independently a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide;
• X is alkyl, alkoxy, thioalkoxy, amino, alkyl amino, or dialkylamino when the phosphorous-containing intersubunit linkage is uncharged at physiological pH;
• and
• X is piperazynyl when the phosphorous-containing intersubunit linkage is charged at physiological pH,
• wherein the antisense oligonucleotide compound:
• (i) comprises at least one phosphorous-containing intersubunit linkage which is charged at physiological pH;
• (ii) contains between 12-40 base-pairing moieties;
• (iii) comprises a targeting sequence of at least 12 contiguous base-pairing moieties complementary to SEQ ID NO:1;
• and
• (iv) optionally comprises a hydrophilic polymer for enhancing the solubility of the antisense oligonucleotide compound;
• and
• (b) by said exposing, forming a heteroduplex structure composed of the virus' vRNA or vcRNA strand and the antisense oligonucleotide compound, wherein the heteroduplex structure has a Tm of dissociation of at least 45° C.

An antisense oligonucleotide compound comprised of morpholino subunits and phosphorous-containing intersubunit linkages having the following structure (I):

• wherein:
• Y1=O;
• Z=O;
• Pi and Pj are independently a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide;
• X is alkyl, alkoxy, thioalkoxy, amino, alkyl amino, or dialkylamino when the phosphorous-containing intersubunit linkage is uncharged at physiological pH;
• and
• X is piperazynyl when the phosphorous-containing intersubunit linkage is charged at physiological pH,
• wherein the antisense oligonucleotide compound:
• (i) comprises at least one phosphorous-containing intersubunit linkage which is charged at physiological pH;
• (ii) contains between 12-40 base-pairing moieties;
• (iii) comprises a targeting sequence of at least 12 contiguous base-pairing moieties complementary to SEQ ID NO:1;
• and
• (iv) optionally comprises a hydrophilic polymer for enhancing the solubility of the antisense oligonucleotide compound;
• and
• wherein the antisense oligonucleotide compound is capable of binding to vRNA/vcRNA or mRNA strands of an Arenavirus in the Arenaviridae family to form a heteroduplex structure having by a Tm of dissociation of at least 45° C.