Methods of treating influenza viral infections

A method of treating an influenza viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a nordihydroguaiaretic acid (NDGA) derivative of the general formula (II) or a pharmaceutically acceptable salt thereof:

• wherein R14, R15, R16 and R17 each independently represents —OH, —OCH3, —O(C═O)CH3, or an unsubstituted or substituted amino acid residue or pharmaceutically acceptable salt thereof, R18 and R19 each independently represents —H or a lower alkyl;
• with the proviso that R14, R15, R16 and R17 are not simultaneously —OH.

A method of treating an avian influenza viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a nordihydroguaiaretic acid (NDGA) derivative of the general formula (III) or a pharmaceutically acceptable salt thereof:

• wherein R20, R21, R22 and R23 each independently represents —OH, —OCH3, —O(C═O)CH3, or an unsubstituted or substituted amino acid residue or pharmaceutically acceptable salt thereof, with the proviso that R20, R21, R22 and R23 are not simultaneously —OH.

A method of treating an influenza viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a catecholic butane selected from the group consisting of tri-O-methyl nordihydroguaiaretic acid (NDGA), tetra-O-methyl NDGA, tetra-glycinyl NDGA, tetra-dimethylglycinyl NDGA, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

A method of treating a subtype H5N1 influenza viral infection in a human subject, comprising orally administering to the human subject a therapeutically effective amount of a nordihydroguaiaretic acid derivative of the general formula (III) or pharmaceutically acceptable salt thereof, in an amount of about 0.01 to about 400 mg/kg of body weight per dose:

• wherein R20, R21, R22 and R23 each represents —OCH3.

A method of inhibiting the induction of a proinflammatory cytokine in a cell by an influenza viral infection, comprising administering to the cell an effective amount of a catecholic butane of the general formula I or a pharmaceutically acceptable salt thereof:

• wherein R1 and R2 each independently represents a hydrogen, a lower alkyl, a lower acyl, an alkylene, or —OR1 and —OR2 each independently represents an unsubstituted or substituted amino acid residue or pharmaceutically acceptable salt thereof;
• R3, R4, R5, R6, R10, R11, R12 and R13 each independently represents a hydrogen, or a lower alkyl;
• and R7, R8 and R9 each independently represents a hydrogen, —OH, a lower alkoxy, a lower acyloxy, an unsubstituted or substituted amino acid residue or salt thereof, or any two adjacent groups together may be an alkyene dioxy.

A method of inhibiting the induction of a pro-inflammatory lipid mediator in a cell by an influenza viral infection, comprising administering to the cell an effective amount of a catecholic butane of the general formula I or a pharmaceutically acceptable salt thereof:

• wherein R1 and R2 each independently represents a hydrogen, a lower alkyl, a lower acyl, an alkylene, or —OR1 and —OR2 each independently represents an unsubstituted or substituted amino acid residue or pharmaceutically acceptable salt thereof;
• R3, R4, R5, R6, R10, R11, R12 and R13 each independently represents a hydrogen, or a lower alkyl;
• and R7, R8 and R9 each independently represents a hydrogen, —OH, a lower alkoxy, a lower acyloxy, an unsubstituted or substituted amino acid residue or salt thereof, or any two adjacent groups together may be an alkyene dioxy.

A method of inhibiting the induction of tumor necrosis factor alpha (TNF-α) in a macrophage cell by a subtype H5N1 influenza viral infection, comprising administering to the macrophage cell an effective amount of a nordihydroguaiaretic acid derivative of the general formula (III) or pharmaceutically acceptable salt thereof:

• wherein R20, R21, R22 and R23 each represents —OCH3.

A method of inhibiting the induction of prostaglandin E2 (PGE2) in a macrophage cell by a subtype H5N1 influenza viral infection, comprising the step of administering to the macrophage cell an effective amount of a nordihydroguaiaretic acid derivative of the general formula (III) or pharmaceutically acceptable salt thereof:

• wherein R20, R21, R22 and R23 each represents —OCH3.