Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Witvrouw, Myriam; Desmyter, Jan; Clercq, Erik De

doi:10.1177/095632029400500601

Cited by 101 publications

(51 citation statements)

References 96 publications

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“…Polyanionic substances such as sulfated polysaccharides (dextran sulfate, pentosan polysulfate, carrageenans, and other polysaccharides extracted from seaweeds) are known for their inhibitory effects on enveloped viruses, including human immunodeficiency virus (HIV), HSV, and CMV, as well as VSV, respiratory syncytial virus, togaviruses, and arenaviruses (2,113). The antiviral activity spectrum of these sulfated polymers (Fig.…”

Section: Polyanionic Substancesmentioning

confidence: 99%

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

2001

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Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5′-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2′-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients

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Section: Polyanionic Substancesmentioning

confidence: 99%

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

2001

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“…Several polyanionic compounds inhibit HIV-1 replication by preventing the binding of the virus to target cells (16). Some of these compounds, including unmodified heparin, heparan sulfate, and suramin-like distamycin A derivatives, although not dextran sulfate, ␤-cyclodextrin, chemically desulfated or low molecular weight heparins, also bind extracellular Tat and inhibit its biological activity in vitro (9,10,14,17) and in vivo (18).…”

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confidence: 99%

Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Rusnati¹,

Urbinati²,

Caputo³

et al. 2001

Journal of Biological Chemistry

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“…Also, these results suggest that the antiviral activity of the protein bound polysaccharide is related to the net electrical charge. It is known that the antiviral activities of polysaccharides increase with the molecular weight or the degree of sulfation (Witvrouw et al, 1994). Therefore, the antiherpetic activity of GLPG would be expected to be enhanced by sulfation or partial digestion.…”

Section: Discussionmentioning

confidence: 99%

Possible Mechanism Underlying the Antiherpetic Activity of a Proteoglycan Isolated from the Mycelia of Ganoderma lucidum in Vitro

Li¹,

Liu²,

Zhao³

2005

BMB Reports

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GLPG (Ganoderma lucidum proteoglycan) was a bioactive fraction obtained by the liquid fermentation of the mycelia of Ganoderma lucidum, EtOH precipitation, and DEAEcellulose column chromatography. GLPG was a proteoglycan with a carbohydrate: protein ratio of 10.4: 1. Its antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were investigated using a cytopathic inhibition assay. GLPG inhibited cell death in a dosedependent manner in HSV-infected cells. In addition, it had no cytotoxic effect even at 2 mg/ml. In order to study the mode of action of the antiviral activity of GLPG, cells were treated with GLPG before, during, and after infection, and viral titer in the supernatant of cell culture 48 h post-infection was determined using a TCID 50 assay. The antiviral effects of GLPG were more remarkable before viral treatment than after treatment. Although the precise mechanism has yet to be defined, our work suggests that GLPG inhibits viral replication by interfering with the early events of viral adsorption and entry into target cells. Thus, this proteoglycan appears to be a candidate anti-HSV agent.

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Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Cited by 101 publications

References 96 publications

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Possible Mechanism Underlying the Antiherpetic Activity of a Proteoglycan Isolated from the Mycelia of Ganoderma lucidum in Vitro

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