Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins.
Sulfated polysaccharides (i.e., dextran sulfate) and sulfated polymers (i.e., sulfated polyvinylalcohol and sulfated copolymers of acrylic acid with vinylalcohol) were found to be potent and selective inhibitors of the replication of respiratory syncytial virus (RSV) and influenza virus type A (influenza A virus) but not of other myxoviruses (parainfluenza 3, measles, and influenza B viruses). The compounds were also inhibitory to human immunodeficiency virus type 1 (HIV-1) and HIV-2 and simian immunodeficiency virus but not simian AIDS-related virus. The mode of antiviral action of the sulfated polysaccharides and polymers can be attributed to an inhibition of virus binding to the cells (HIV-1), inhibition of virus-cell fusion (influenza A virus), or inhibition of both virus-cell binding and fusion (RSV). The fact that the sulfated polysaccharides and polymers are inhibitory to some myxoviruses and retroviruses but not to others seems to depend on the composition of the amino acid sequences of the viral envelope glycoproteins that are involved in virus-cell binding and fusion. All myxoviruses and retroviruses that are sensitive to the sulfated polysaccharides and polymers share a tripeptide segment (Phe-Leu-Gly). This tripeptide segment may be involved either directly (as a target sequence) or indirectly in the inhibitory effects of the compounds on virus-cell binding and fusion.
Hosoya
M
M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Balzarini
J
J
Shigeta
S
S
De Clercq
E
E
D000180:Acrylic Resins / Q000494:pharmacology; D000595:Amino Acid Sequence; D016264:Dextran Sulfate / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000187:drug effects*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D012190:Retroviridae / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000180:Acrylic Resins; C063252:sulfated acrylic acid-vinyl alcohol copolymer; C063253:sulfated polyvinyl alcohol; D010426:Pentosan Sulfuric Polyester; D006493:Heparin; D016264:Dextran Sulfate