Dextran sulfate inhibits the fusion of influenza virus with model membranes, and suppresses influenza virus replication in vivo

Lüscher-Mattli, Madeleine; Glück, Reinhard

doi:10.1016/0166-3542(90)90064-e

Cited by 41 publications

(16 citation statements)

References 23 publications

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“…As demonstrated previously by Baba et al (3), Mitsuya et al (19), Schols et al (22), and Nakashima et al (20), dextran sulfate interferes with the HIV replicative cycle at the virus-cell binding step. Our present findings, as well as the recent findings of Luscher-Mattli and Gluck (18), who demonstrated that dextran sulfate inhibits fusion of influenza A virus with liposomal membranes, indicate that the inhibitory effect of dextran sulfate on the replication of myxoviruses is due to specific inhibition of virus-cell fusion rather than virus-cell binding (adsorption).…”

Section: Resultssupporting

confidence: 86%

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

Hosoya

Balzarini

Shigeta

et al. 1991

Antimicrob Agents Chemother

126

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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.

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Section: Resultssupporting

confidence: 86%

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

Hosoya

Balzarini

Shigeta

et al. 1991

Antimicrob Agents Chemother

126

View full text Add to dashboard Cite

show abstract

“…In contrast, they do not inhibit the adsorption of influenza A virus (Table 3). Our present findings as well as the findings of Luscher-Mattli (11), who demonstrated that dextran sulfate inhibits fusion of influenza A virus with liposomal membranes, indicate that the inhibitory effect of the sulfonic acid polymers on the replication of influenza A virus is due to a specific inhibition of virus-cell fusion rather than virus-cell binding (adsorption).…”

Section: Discussionsupporting

confidence: 85%

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

Ikeda

Neyts

Verma

et al. 1994

Antimicrob Agents Chemother

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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.

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“…In general, polyanionic compounds exhibit their anti-HIV activity by binding to the V3 domain of gp120 (Baba et al, 1988b;Nakashima et al, 1989;Schols et al, 1991, 1992, Witvrouw et al, 1994. Although the polyanions inhibit the binding of herpesviruses and HIV, and thus indirectly prevent the subsequent fusion process as well, their effects on the replication of influenza virus can be ascribed primarily to inhibition of virus-cell fusion (Lüscher-Mattli & Glück, 1990;Ikeda et al, 1994). The most antivirally effective phenolic polymers were the different salt forms of KOP (sodium-, ammonium-, potassium salt) as well as the copolymers containing KOP (KHYKOP, KGALOP).…”

Section: Discussionmentioning

confidence: 99%

In vitro Activity of Polyhydroxycarboxylates against Herpesviruses and Hiv

Meerbach

Neyts

Balzarini

et al. 2001

Antivir Chem Chemother

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The antiviral activity of 17 polyhydroxycarboxylates derived from phenolic compounds was evaluated against herpesviruses and HIV. When present during virus adsorption several of the polymers exhibited potent activity against herpes simplex virus type 1 (HSV-1), HSV-2, thymidine kinase deficient HSV-1, human cytomegalovirus (HCMV) and HIV-1 and HIV-2 at concentrations that were not toxic to the host cells. A close correlation was found between the 50% inhibitory concentrations of the polyhydroxycarboxylates against HCMVinduced cytopathicity, their inhibitory effect on the expression of HCMV-specific immediate early antigens and their inhibitory effects on HCMV adsorption to the cells. The antiviral activity of the phenolic polymers was dependent on the presence of a sufficient number of carboxylic groups. The mechanism of antiviral action of the polyhydroxycarboxylates can thus be ascribed to inhibition of virus adsorption. This type of compound may have potential in a vaginal gel to prevent sexual transmission of HSV and HIV.

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Dextran sulfate inhibits the fusion of influenza virus with model membranes, and suppresses influenza virus replication in vivo

Cited by 41 publications

References 23 publications

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

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

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

In vitro Activity of Polyhydroxycarboxylates against Herpesviruses and Hiv

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