Anti-HSV

SAR studies were carried out by de Bruyne et al. [92] on a series of dimeric procyanidins, considered as model compounds for antiviral therapies. On the whole, proanthocyanidins containing EC dimers exhibited more pronounced activity against herpes simplex virus (HSV) and human immunodeficiency virus (HIV), while the presence of ortho-trihydroxyl groups in the B-ring appeared to be essential in all proanthocyanidins exhibiting anti-HSV effects. Galloylation and polymerization reinforced the antiviral activities markedly. 

PM Hughes, AK Mitra. (1993). Effect of acylation on the ocular disposition of acyclovir. II Corneal permeability and anti-HSV 1 activity of 2 -esters in rabbit epithelial keratitis. J Ocular Pharmacol 9 299-309. 

The protein A (pA), antihuman serum albumin (a-HSA, M 150 kD), and human serum albumin (HSA, M 65 kD) were provided by Paradocs BV (Tiel, The Netherlands). The Herpes Simplex Virus type 1 (HSV-1) and anti-HSV-1 gG glycoprotein G monoclonal antibody (a-HSV-1 gG) were purchased from Virusys Corporation (Marriottsville, MD, USA). Bovine serum albumin (BSA, M 50 kD) was purchased from Sigma-Aldrich Chemie BV (Zwijndrecht, The Netherlands). Synthetic surface protein of Hepatitis-B virus generated in Hep-G2 cell-line (HEP G2, M 25 kD) was provided by BioMerieux BV (Boxtel, The Netherlands). Phosphate buffered saline (PBS) was used for all experiments. 

Fig. 10.15 Virus detection test. Sensor signal (phase change) measured between channel 1 and the reference channel for the immobilization of anti HSV 1 glycoprotein G monoclonal antibody layer on the sensing surface of channel 1 (A HSV i gG) and the binding of HSV 1 particles to this layer (A IISV i). Reprinted from Ref. 28 with permission. 2008 American Chemical Society...

Table 5. Anti-HSV-1 Activity, Cytotoxicity and Selectivity Index...

Soyasaponin I and II were studied in vitro against herpes simplex virus type I (HSV-1). Soyasaponin II was more potent than soyasaponin I in the reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. This activity was not due to the inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus [160]. Astragaloside II afforded almost 100% protection of T-lymphocytes in vitro against the cytophatic effects of HIV infection. However, the EC50 of ca. 2.5 x 105 molar was difficult to achieve in vivo [98],... 

Three oral agents are licensed for the treatment of HSV and VZV infections acyclovir, valacyclovir, and famciclovir. They have similar mechanisms of action and similar indications for clinical use all are well tolerated. Acyclovir, licensed first, has been the most extensively studied in addition, it is the only anti-HSV agent available for intravenous use in the United States. Neither valacyclovir nor famciclovir have been fully evaluated in pediatric patients thus, they are not indicated for the treatment of varicella infection. 

Jenssen, H., Gutteberg, T.J., and Lejon, T. (2005) Modeling of anti-HSV activity of lactoferricin analogues using amino acid descriptors. J. Pept. Sci. 11,97-103. 

P. Mandal, C. A. Pujol, E. B. Damonte, T. Ghosh, and B. Ray, Xylans from Scinaia hater. Structural features, sulfation and anti-HSV activity, Int. J. Biol. Macromol., 46 (2010) 173-178. 

Hydroxymanzamine A was isolated from the Indonesian sponge PachypeUina sp. with moderate antitumor and anti-HSV-II activity, in 1994 ]39]. It was named as manzamine Gin some literature ]20]. 6-Hydroxymanzamine A (called manzamine Y in some references [20,41]) and 3,4-dihydromanzamine A were isolated from the Okinawan marine sponge Amphimedon sp. The Philippine sponge Xestospongia (=Acanthostrongylophora) ashmorica Hooper yielded manzamine A N-oxide, 3,4-dihydromanzamine A N-oxide, and 6-deoxymanzamine X ]10]. 

Antiviral activity has been demonstrated mainly for A. membranaceus, that represents the most studied species, expecially against Coxsackie viruses [234] but also against different kinds of viral infections. "Astragali radix" extracts show protective effects against Japanese Encephalitis Vitus (JEV) infection in mice both by oral and infraperitoneal injection this effect is based on a non-specific mechanism during the early stage of injection, before it shifts to antibody production. A. membranaceus (AM) shows curative effects on the mice infected with Herpes Simplex Virus type-1 (HSV-1) when somministated with acyclovir (ACV) [329]. The anti-HSV activity of suppository and ointment forms of AM combined... 

In order to find new sources of antiviral agents with different mechanisms of action, extracts of marine algae from all over the world were assayed for anti-HSV activity. The first screening of 89 types of seaweed collected from British Columbia, Canada and Korea for antiviral activity was reported by Kim et al. [66]. Analipus japonicus was the most potent anti-herpes algae. Extracts from 13 types of Korean seaweed previously shown to contain antiviral activity were investigated in more detail in order to learn their mechanism of action [14]. Four species, Enteromorpha linza, Colpomenia bullosa, Scytosiphon lomentaria and Undaria pinnatifida were active against HSV. In experiments to determine the site of action of these antiviral extracts, the predominant activity was virucidal (i.e., direct inactivation of virus particles) rather than inhibition of virus replication. 

The anti-HSV-1 activity of Ca-SP was assessed by plaque yield reduction and compared with those of dextran sulphate as a representative sulphated PS. These data indicate that Ca-SP is a potent antiviral agent against HSV-1, as even at low concentrations of Ca-SP, no enhancement of virus-induced syncytium formation was observed, as occurred in dextran sulphate-treated cultures. Reeently, Lee et al. [73] investigated the effects of structural modifications of Ca-SP on antiviral activity. Calcium ion binding with the anionic part of the molecule was replaeed with various metal cations, and their inhibitory effects on the replication of HSV-1 were evaluated. Replacement of calcium ion with sodium and potassium ions maintained the antiviral activity, while divalent and trivalent metal cations reduced the activity. Depolymerization of sodium spirulan with hydrogen peroxide decreased the antiviral activity as its molecular weight decreased. 

The cell-wall sulphated PS of the red microalga Porphyridium spp. also appears to be a good candidate for the development of an anti-HSV drug [74,75]. Treatment of cells with 1 pg/ml PS resulted in 50% inhibition of HSV infection as measured by the plaque assay. Inhibition of the production of new viral particles was also shown when pre-infected cell cultures were treated with the PS. It seems therefore that the PS is able to inhibit viral infection by preventing adsorption of the virus into the host cells and/or by inhibiting the production of new viral particles inside the host cells. The cell-wall sulphated PS of this red microalga Porphyridium spp. also had impressive antiviral activity against VZV [74]. 

Other anti-HSV sulphated PS included sulphated galactans from the marine alga Bostrychia montagnei [89], the red seaweed Pterocladia capillacea [90], extracts of Cryptopleura ramosa and Nothogenia fastigiata, two red seaweeds from the South American coast [91,92], and fucoidans from the brown seaweed utricularis [93]. 

Besides sulphated PS, reports on anti-HSV compounds isolated from marine algae are recorded in the literature. Specimens of the brown alga Dictyota pfaffii from Atol das Rocas, northeast Brazil, afforded the rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2,6-dolabella-diene and the new 10-acetoxy-8,18-dihydroxy-2,6-dolabella-diene [46]. These substances showed strong anti-HSV-1 activity in vitro. Several antiviral diterpenes were isolated from other brown algae of the Dictyota genus. 

Other marine organisms and microorganisms in addition to marine algae have been reported to produce anti-HSV compounds, including terpenoids, steroids, alkaloids, peptides and sulphated PS. 

Marine sponges have been shown to be a prolific source of anti-HSV alkaloids. Dragmacidin F, Fig. (6) is a new antiviral bromoindole alkaloid isolated from the Mediterranean sponge Halicortex spp. collected from the south coast of Ustica Island, Italy [56]. This compound. 

A marine Pseudomonas species WAK-1 produced extracellular glycosaminoglycan and showed anti-HSV-1 activity in RPMI 8226 cells [105], while the water-soluble fraction of the marine diatom Haslea ostrearia delayed HSV-1-induced syncitia formation [17]. A novel acid PS, nostoflan, was isolated from the cyanobacterium Nostoc jlagelliforme, which had a broad antiviral spectrum against enveloped viruses, including HSV-1 and HSV-2, whose cellular receptors are carbohydrates [106]. Two new... 

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