In vitro antiviral activity of polyoxotungstate (PM-19) and other polyoxometalates against herpes simplex virus

Fukuma, Mariko; Seto, Yoshiko; Yamase, Toshihiro

doi:10.1016/0166-3542(91)90047-u

Cited by 58 publications

(33 citation statements)

References 24 publications

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“…Several studies have indicated that certain paM are significantly inhibitory to human immunodeficiency virus (HIV) in vitro (Hill et al, 1990(Hill et al, , 1993Yamamoto et al, 1992;Inouye et al, 1993;Blasecki, 1994;Judd et al, 1994;Kim et al, 1994;Swart & Meijer, 1994;Moore etal., 1995;Shigeta et al, 1995). Herpesviruses have been reported to be inhibited by some of these compounds both in vitro (Fukuma et al, 1991;Yamamoto et al, 1992;Ikeda et al, 1993) and in vivo (Ikeda et al, 1994). Other viruses inhibited include toga-, rhabdo-, arena-, paramyxo-and murine retroviruses (Yamamoto et al, 1992;Ikeda et al, 1993;Shigeta et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

Huffman

Sidwell

Barnard

et al. 1997

Antivir Chem Chemother

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A series of germanium- or silicon-centred heteropolytungstates (polyoxometalates) with the Barrel, Keggin or double Keggin structure were evaluated in vitro for their effects against influenza A (IV-A) and B (IV-B) viruses. Their 50% effective concentrations (EC50) against recent isolates of IV-A (H1N1) and IV-B ranged from 0.1 to 7.8 μM against IV-A (H3N2), the EC50 concentrations were often 10-fold higher. Recent clinical isolates of IV-A were generally more susceptible to these antiviral effects than older, laboratory-adapted strains. These experiments used inhibition of viral CPE in MDCK cells as determined microscopically and by Neutral Red (NR) uptake. Virus yield reduction studies indicated the 90% effective concentrations (EC90) ranged from 0.2 to 32 μM against these viruses. Cytotoxic or cell inhibitory concentrations (CC50), determined by NR uptake and total cell count, ranged from 38 to 189 μM, indicating high selective indices for some of these compounds. Altering time of addition of an active compound relative to infecting cells with IV-A (HINl) showed greatest efficacy when given early in viral replication. Five of the most active polyoxometalates were evaluated against IV-B infections in mice using intraperitoneal treatment beginning 4 h prior to virus exposure. Two of the compounds, one with the Barrel structure and the other with a double Keggin structure, were particularly inhibitory, preventing deaths, reducing arterial oxygen decline and lowering lung consolidation. Lung virus titres were reduced by a maximum of 0.7 log10. Therapy initiated 8 h post-virus exposure was not effective against this in vivo infection.

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Section: Introductionmentioning

confidence: 99%

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

Huffman

Sidwell

Barnard

et al. 1997

Antivir Chem Chemother

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“…Attachment of HSV can be inhibited by heparin, which competes directly with the binding of gC and gB to cell surface heparan sulfate (HS) on cells (23,24,(26)(27)(28). Other polymeric anions and polyoxotungstate compounds have been shown to inhibit attachment (13,19,25,26,35,40). Preventing entry is also a viable strategy for blocking initial HSV infection.…”

mentioning

confidence: 99%

“…The HSV gD protein binds to one of four types of cellular coreceptors, and the soluble ectodomain of gD inhibits fusion by competing for binding to these receptors (20,37). The soluble ectodomains of the cellular receptors have also been reported to prevent entry (19,38). Although these soluble ectodomains inhibit fusion in cell culture, they have not been tested in vivo.…”

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confidence: 99%

Addition of a C-Terminal Cysteine Improves the Anti-Herpes Simplex Virus Activity of a Peptide Containing the Human Immunodeficiency Virus Type 1 TAT Protein Transduction Domain

Bultmann¹,

Teuton

Brandt

2007

Antimicrob Agents Chemother

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Previous studies have shown that peptides containing the protein transduction domain (PTD) of the human immunodeficiency virus tat protein (GRKKRRQRRR) were effective inhibitors of herpes simplex virus type 1 (HSV-1) entry (H. Bultmann and C. R. Brandt, J. Biol. Chem. 277:36018-36023, 2002). We now show that the addition of a single cysteine residue to the C terminus of the TAT PTD (TAT-C peptide) improves the antiviral activity against HSV-1 and HSV-2. The principle effect of adding the cysteine was to enable the peptide to inactivate virions and to induce a state of resistance to infection in cells pretreated with peptide. The TAT-C peptide acted extracellularly, immediately blocked entry of adsorbed virus, prevented VP16 translocation to the nucleus, and blocked syncytium formation and cell-cell spread. Thus, TAT-C peptides are fusion inhibitors. The induction of the resistance of cells to infection was rapid, recovered with a half-life of 5 to 6 h, and could be reinduced by peptide treatment. TAT-C bound to heparan sulfate but was a poor competitor for viral attachment. The antiviral activity depended on the net positive charge of the peptide but not on chirality, and a free sulfhydryl group was not essential for antiviral activity because TAT-C dimers were at least as effective as monomers. The unique combination of antiviral activities and low toxicity combine to make TAT-C a strong candidate for further development as a drug to block HSV infection.Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are widespread human pathogens. Between 70 and 90% of adults in the United States are infected with HSV-1, and 22% of individuals over the age of 12 are seropositive for HSV-2 (7, 61). Both viruses infect mucous membranes causing ulcerative lesions that are usually self-limited in immunocompetent individuals. However, serious infections can occur, including lethal neonatal HSV, encephalitis, and blinding keratitis (34,61). A number of antivirals are approved for HSV treatment, and the use of these drugs has had a significant impact on the disease. These antivirals reduce the frequency of recurrent viral shedding and disease and reduce transmission of genital herpes between discordant partners (12,42,46). Although these treatment regimens significantly reduce disease, they are not completely effective and cannot clear latent infections. One significant problem in dealing with HSV infections is the ability of the virus to persist in the host in the form of latent infection (45). Preventing the establishment of a persistent infection, which could be accomplished either by blocking the initial infection or preventing the establishment of latency, would be ideal for dealing with this virus.One strategy for preventing infection is to block the attachment of virus. Attachment of HSV can be inhibited by heparin, which competes directly with the binding of gC and gB to cell surface heparan sulfate (HS) on cells (23,24,(26)(27)(28). Other polymeric anions and polyoxotungstate compounds have been shown to inhibit attachm...

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“…And the presence of PM-19 (over 10 Ìg/ml) completely inhibited the production of plaques. We have shown that PM-19 inhibits replication at an early stage, such as viral adsorption by or viral penetration of cells, and that it also decreases virus-specific incorporation of 3 H-thymidine by cells [4].…”

Section: Introductionmentioning

confidence: 85%

“…Plaque assays were performed according to a method described previously [4]. Virus titers are expressed as plaque-forming units (PFU) and results are expressed as the number of plaques or as plaque inhibition (% of control).…”

Section: Plaque Assaymentioning

confidence: 99%

Mechanism of the Protective Effect of Heteropolyoxotungstate against Herpes Simplex Virus Type 2

et al. 2003

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The effects of heteropolyoxotungstate (K₇[PTi₂W₁₀O₄₀]· 6H₂O; PM-19) on the replication of herpes simplex virus type 2 (HSV-2) were examined using a semiquantitative polymerase chain reaction of intracellular viral DNA established by us and also other methods. Vero cells were infected with HSV-2 strains: either the standard strain 169, or the acyclovir-resistant strain YS-4C-1. PM-19 was added at various stages during the replication of HSV-2. PM-19 strongly inhibited the synthesis of viral genomic DNA when it was added at the time of infection. The addition of PM-19 60–90 min after viral inoculation time-dependently decreased the antiviral activity and increased the relative yield of viral DNA, and the addition of PM-19 was completely ineffective at times later than 90 min. These results suggested that PM-19 inhibited viral penetration but did not affect the synthesis of viral DNA. Furthermore, PM-19 strongly inhibited a second round of infection.

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In vitro antiviral activity of polyoxotungstate (PM-19) and other polyoxometalates against herpes simplex virus

Cited by 58 publications

References 24 publications

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

Addition of a C-Terminal Cysteine Improves the Anti-Herpes Simplex Virus Activity of a Peptide Containing the Human Immunodeficiency Virus Type 1 TAT Protein Transduction Domain

Mechanism of the Protective Effect of Heteropolyoxotungstate against Herpes Simplex Virus Type 2

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