Antiviral effects of single-stranded polynucleotide inhibitors of the influenza virion-associated transcriptase against influenza virus infection of hamsters and ferrets

Abstract

Administration of a single-stranded polynucleotide copolymer containing 9% cytidine residues and 91% 4-thiouridine residues [poly(C,S 4U 10)], a known potent inhibitor of the virion transcriptase of influenza viruses, suppressed the amount of virus recoverable from the nasal washes of influenza virus-infected hamsters and ferrets. The incidence of sneezing and nasal discharge in infected ferrets was also reduced. In hamsters, poly(C,S 4U 10) was more effective than amantadine-HCl given at a 5-fold higher dose; in ferrets, its effect was comparable with amantadine-HCl or Virazole. Polyinosinic acid in combination with poly-5-hydroxy cytidylic acid also had anti-influenza effects. Poly(C,S 4U 10) annealed to polyadenylic acid was not effective, nor was the double-stranded polymer (polyinosinic acid) · (polycytidylic acid), even when complexed with carboxymethylcellulose and polylysine. No toxic effects of poly(C,S 4U 10) were apparent in the treated hamsters and ferrets, and high doses (≥ 2.86 g/kg) administered intraperitoneally to mice produced no adverse effects.