IN-VITRO AND IN-VIVO INHIBITION OF ORTHOMYXOVIRUS AND PARAMYXOVIRUS INFECTIONS BY A NEW CLASS OF SULFONIC-ACID POLYMERS INTERACTING WITH VIRUS-CELL BINDING AND OR FUSION/

A series of sulfonic acid polymers were shown to be potent and selecti ve inhibitors of respiratory syncytial virus (RSV) and influenza A vir us. The compounds inhibit the replication of RSV and influenza A virus in HeLa and MDCK cells, at concentrations of 0.16 and 4.0 mu g/ml, re spectively, and are nontoxic to growing cells at concentrations of >10 0 mu g/ml. The mode of antiviral action of the sulfonic acid polymers can be ascribed to inhibition of virus-cell fusion (for influenza A vi rus) or inhibition of both virus-cell binding and fusion (for RSV). Th e sulfonic acid prototype PAMPS [poly(2-acrylamido-2-methyl-1-propanes ul acid)l, when administered intranasally to mice as a single dose of 10 or 50 mg per kg of body weight at the time of infection, completely inhibited influenza A virus replication (in lungs) and virus-associat ed lung consolidation in immunocompetent mice and completely protected NMRI and SCID (severe combined immune deficiency) mice against influe nza A virus-associated mortality. When administered 1 h before or afte r virus inoculation, no protective effect was observed at a dose of 10 or 100 mg/kg. Sulfonic acid polymers exert selective inhibitory effec ts on RSV and influenza A virus replication.