In vitro and in vivo inhibition of ortho- 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 selective inhibitors of respiratory syncytial virus (RSV) and influenza A virus. The compounds inhibit the replication of RSV and influenza A virus in HeLa and MDCK cells, at concentrations of 0.16 and 4.0 micrograms/ml, respectively, and are nontoxic to growing cells at concentrations of > 100 micrograms/ml. The mode of antiviral action of the sulfonic acid polymers can be ascribed to inhibition of virus-cell fusion (for influenza A virus) or inhibition of both virus-cell binding and fusion (for RSV). The sulfonic acid prototype PAMPS [poly(2-acrylamido-2-methyl-1-propanesulfonic acid)], 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-associated lung consolidation in immunocompetent mice and completely protected NMRI and SCID (severe combined immune deficiency) mice against influenza A virus-associated mortality. When administered 1 h before or after virus inoculation, no protective effect was observed at a dose of 10 or 100 mg/kg. Sulfonic acid polymers exert selective inhibitory effects on RSV and influenza A virus replication.
Ikeda
S
S
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Neyts
J
J
Verma
S
S
Wickramasinghe
A
A
Mohan
P
P
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000517:prevention & control; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D013451:Sulfonic Acids / Q000494:pharmacology*
D000998:Antiviral Agents; D011108:Polymers; D011991:Receptors, Virus; D013451:Sulfonic Acids; C077118:poly(2-acrylamido-2-methyl-1-propanesulfonic acid)