Anti-Herpes Simplex Virus Activities of Two Novel Disulphated Cyclitols

Ekblad, Maria; Bergström, Tomas; Banwell, Martin G.; Bonnet, Muriel; Renner, Jens; Ferro, Vito; Trybala, Edward

doi:10.1177/095632020601700205

Cited by 21 publications

(18 citation statements)

References 20 publications

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“…Attachment and penetration assays -The attachment assay followed procedures that have been described previously (Ekblad et al 2006) with minor modifications. Different concentrations of GA or PG were mixed with purified radiolabelled HSV-1 and incubated for 15 min at 37°C.…”

Section: Screening Of In Vitro Anti-hsv-1 Activity -Confluentmentioning

confidence: 99%

“…After 72 h, cells were fixed and stained with naphtol blue-black and plaques were counted. The IC 50 was defined as the concentration (µM) that inhibited 50% of viral plaque formation when compared to untreated controls.Virucidal assay -This assay followed procedures that have been previously described (Ekblad et al 2006). Mixtures of GA or pentyl gallate (PG) and 4.0 x 10 4 PFU of HSV-1 in serum-free MEM were co-incubated for 20 min at 37°C in a water bath prior to the dilution of the mixture to non-inhibitory concentrations of compound (1:100), and the residual infectivity was determined by a viral plaque number reduction assay, as described above.…”

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confidence: 99%

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Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate

Kratz¹,

Andrighetti-Fröhner²,

Kolling³

et al. 2008

Mem. Inst. Oswaldo Cruz

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114

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The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. The inhibitory effects of GA and 15 gallates on Herpes Simplex Virus type 1 (HSV-1) and Human Immunodeficiency Virus (HIV-1) replication were investigated here. After a preliminary screening of these compounds, GA and pentyl gallate (PG) seemed to be the most active compounds against HSV-1 replication and their mode of action was characterized through a set of assays, which attempted to localize the step of the viral multiplication cycle where impairment occurred. The detected anti-HSV-1 activity was mediated by the inhibition of virus attachment to and penetration into cells, and by virucidal properties. Furthermore, an anti-HIV-1 activity was also found, to different degrees. In summary, our results suggest that both compounds could be regarded as promising candidates for the development of topical anti-HSV-1 agents, and further studies concerning the anti-HIV-1 activity of this group of molecules are merited.Key words: antiviral -HSV-1 -HIV-1 -gallic acid -pentyl gallate Herpes Simplex Virus type 1 (HSV-1) is an enveloped DNA virus that causes one of the most common viral infections in humans, leading to a variety of diseases ranging from mild to severe and sometimes life-threatening (White & Fenner 1994, Whitley & Rozman 2001. Although several nucleoside analogues have been approved for clinical use, such as acyclovir, immunocompromised patients are at increased risk of severity and recurrent infections, since resistant strains have recently been observed (Brady & Bernstein 2004). Therefore, it is desirable to develop new antiviral agents in order to substitute or complement currently available drugs.The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by the food and pharmaceutical industries (van der Heijden et al. 1986, Kubo et al. 2002a. Besides the antioxidant activity, other biological activities have been described for this group of molecules, mainly anticancer mechanisms (Fiuza et al. 2004, Kitagawa et al. 2005, Frey et al. 2006, Veluri et al. 2006 as well as antibacterial and antifungal properties (Fujita & Kubo 2002, Kubo et al. 2002b, c, 2003, Stapleton et al. 2004). However, there are few reports about the antiviral activity of these compounds. In 1988, a study described the inhibition of HSV-1 and HSV-2 replication by methyl gallate (Kane et al. 1988). In 2002, as part of the screening of phenolic compounds against HIV-1 integrase, GA was found to be active (Ahn et al. 2002). More recently, several biological activities of a group of gallates were described by our research group, and various structure-activity relationships regarding their anti-HSV-1, antioxidant and genotoxic effects were proposed (Savi et al. 2005). Furthermore, the pronounced anti-HSV-1 activity of octyl gallate, and its inhibitory...

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Section: Screening Of In Vitro Anti-hsv-1 Activity -Confluentmentioning

confidence: 99%

mentioning

confidence: 99%

Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate

Kratz¹,

Andrighetti-Fröhner²,

Kolling³

et al. 2008

Mem. Inst. Oswaldo Cruz

Self Cite

114

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“…Virucidal Assay The virucidal assay was performed as described 25,26) with minor modifications. HSV-1 (15577 strain) suspension (4×10 4 PFU) was pre-incubated with or without various concentrations of samples at 37°C for 2 h. Then the mixtures were diluted (1 : 1000) and their residual infectivity was determined by plaque reduction assay.…”

Section: )mentioning

confidence: 99%

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

Shen

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3′-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC 50 values of 2.2, 1.5 and 2.5 µg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles. Following viral penetration, Kuwanon X reduced the expression of HSV-1 IE and L genes, and decreased the synthesis of HSV-1 DNA. Furthermore, it was demonstrated that Kuwanon X inhibited the HSV-1-induced nuclear factor (NF)-κB activation through blocking the nuclear translocation and DNA binding of NF-κB. These results suggest that Kuwanon X exerts anti-HSV activity through multiple modes and could be a potential candidate for the therapy of HSV infection.Key words anti-herpes simplex virus (HSV) activity; Kuwanon X; penetration; gene expression; nuclear factor (NF)-κB; Mulberry Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are prevalent pathogens worldwide. HSV-1 is the main cause of orofacial herpes, cephalitis, corneal blindness, and several disorders of the peripheral nervous system; HSV-2 is usually associated with recurrent genital herpes, meningoencephalitis in neonates and meningitis in adults. Both HSV-1 and HSV-2 can cause latent infections in the neurons system, and then cause lesions at or near the point of entry into the body when they are reactivated.1,2) Recently, it was reported that HSV infections can increase the transmission of human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1).3) During the productive infection, a successful HSV replication cycle is dependent on the completion of several steps, including α (immediate-early or IE), β (early or E), γ (late or L) genes and unpaired DNA replication based on sequential expression. The IE genes, such as UL54, encode transacting regulators of gene expression. The E genes, including UL52, are involved in viral DNA synthesis and nucleotide metabolism. The L genes, mainly encode structural proteins, e.g. ICP5 encoding the main capsid protein VP5. 4)The standard therapy for HSV infections are nucleoside analogues, such as acyclovir (ACV) and penciclovir. However, the emergence of HSV strains resistant to ACV remains an important clinical concern in immunocompromised individuals.5) Therefore, it is necessary to develop new antiherpetic agents with mechanisms of action different from that of nucleoside analogues.Mulberry (Morusalba L.) is widely cultivated in several Asian countries. Its leaves, fruits, twigs and root barks have long been used in Chinese medicine to reduce fever, maintain liver health, improve eyesight and lower blood pressure. Besides, Mulberry leaf is commonly...

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“…28) Virus Inactivation Assay The assay followed the procedures previously described. 29) Mixtures of each compound and 4.0ϫ10 4 PFU of HSV-2 in serum-free EMEM were coincubated for 20 min at 37°C in a water bath prior to the dilution of the mixture to non-inhibitory concentrations of compound (1 : 100), and the residual infectivity was determined by plaque number reduction assay, as described above.…”

Section: Binding Of Purified Virions and Isolated Viral Glycoproteinsmentioning

confidence: 99%

“…29) Briefly, equal volumes (50 ml) of compounds (125 mM) and different dilutions of BSA or FCS solutions were mixed and incubated for 5 min at room temperature prior to the addition of 200 PFU of HSV-2 333 strain in serum-free medium. Additional incubation was then carried out for 15 min at 37°C and the mixtures were then transferred to GMK AH1 cells.…”

Section: Antiviral Activity Of Compounds In the Presence Of Protein-rmentioning

confidence: 99%

Evaluation of Anti-HSV-2 Activity of Gallic Acid and Pentyl Gallate

Kratz

Andrighetti-Fröhner

Leal

et al. 2008

Biological & Pharmaceutical Bulletin

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128

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Herpes simplex virus (HSV) is a DNA-containing enveloped virus that causes common viral infections in humans worldwide leading to a variety of diseases. HSV-1 and HSV-2 can be distinguished on the basis of clinical manifestations (the former is more frequently associated with oral cold sores, while the later causes genital ulcers) and biochemical and serological examinations. In most cases, HSV infection is usually benign or asymptomatic in immunocompetent individuals; however, in patients with an immature or compromised immune system, the infection can be serious and sometimes life-threatening. 1,2) Several nucleoside analogues have been approved for clinical use. Among those, acyclovir is widely used for the systemic treatment of HSV infections. It is a highly selective antiviral agent because it is specifically phosphorylated by viral thymidine kinase in infected cells. However, acyclovir-resistant HSV infection in immunocompromised patients such as transplanted patients and patients with AIDS has recently been observed. Therefore, it is desirable to develop new anti-HSV agents in order to substitute or complement the antiviral drugs available. 3,4)The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. 5,6) Besides the antioxidant activity, other biological activities have been described for this group of molecules, mainly anticancer, 7-10) antibacterial and antifungal properties. [11][12][13][14][15][16] There are few reports about the antiviral activity of these compounds. In 1988, the potent inhibition of HSV-1 and HSV-2 by methyl gallate was described. 17) In 2000, as part of the screening of phenolic compounds against HIV-1 integrase, gallic acid was found to be active. 18)More recently, the anti-HSV activity of several gallates was described by our research group, which proposed various structure-activity relationships regarding the antiviral, antioxidant and genotoxic effects.19) Furthermore, the pronounced anti-HSV-1 activity of octyl gallate, and its inhibitory effect against RNA viruses were also recently described. 20,21) In the present study, the anti-HSV-2 activity of gallic acid and pentyl gallate was evaluated followed by the determination of the site of antiviral activity of these compounds. MATERIALS AND METHODSCompounds GA and pentyl gallate (PG) (Fig. 1) were synthesized as previously described.19) The compounds (50 mM) were dissolved in dimethyl sulfoxide, stored at Ϫ20°C protected from light, and further diluted in culture medium prior to use.Cells and Virus African green monkey kidney cells (GMK AH1) were grown in Eagle's minimum essential medium (EMEM, Gibco BRL, Grand Island, NY, U.S.A.) supplemented with 2% fetal calf serum (FSC), 0.05% primaton substance (Kraft Inc., Norwich, CT, U.S.A.), 100 U/ml Göteborg, Sweden. Received November 23, 2007; accepted February 5, 2008; published online February 20, 2008 The synthetic n-alkyl esters of galli...

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Anti-Herpes Simplex Virus Activities of Two Novel Disulphated Cyclitols

Cited by 21 publications

References 20 publications

Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate

Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

Evaluation of Anti-HSV-2 Activity of Gallic Acid and Pentyl Gallate

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