Herpes simplex virus -type inhibition

A rather distantly related analogue incorporating a 3-di-carbonyl moiety as a bioisosteric replacement for a carboxyl, aril done (55), blocks the uncoating of polio virus and herpes simplex virus type I and thus inhibits infection of cells and l.he early stages of virus replication. Thus effective therapy would require careful timing as it does with amantidine. 

Catechins and proanthocyanidins have a documented antiviral activity. Catechins from an extract of Cocos nucifera husk fibre exhibited a strong inhibitory activity against acyclovir-resistant herpes simplex virus type 1 (HSV-l-ACVr) [62]. The use of 10 to 20ngml of ECG and EGCG has been reported to cause 50% inhibition of human immunodeficiency virus reverse transcriptase [89], while Kara and Nakayama [90] reported that a patented chewing gum containing tea catechins is claimed to prevent viral infections against influenza and to inhibit dissemination of this virus. 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Pharmacology A fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus types 1 and 2, and vaccinia virus. Some strains of adenovirus are also inhibited in vitro. Its antiviral mechanism of action is not completely known. 

Mechanism of Action Penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Therapeutic Effect An antiviral compound that has inhibitory activity against herpes simplex virus types 1 (HSV-1)... 

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],... 

In a recent investigation of phenolic compounds tested, using herpes simplex virus type 1 (HSV-1) infected Vero cells, caffeic acid has been reported to inhibit virus replication [91], In a related study [92], chlorogenic acid significantly inhibited acyclovir-resistant HSV-1 replication without any cytotoxicity. However, flavonoids have exhibited cytotoxicity at the same concentration [92],... 

Peyman, A., Helsberg, M., Kretzschmar, G., Mag, M., Grabley, S. and Uhlmann, E. (1995) Inhibition of viral growth by antisense oligonucleotides directed against the IE110 and the UL30 mRNA of Herpes Simplex Virus Type-1. Biol. Chem. Hoope-Seyler, 376, 195-198. 

Fujihara, T. and Hayashi, K. 1995. Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection to mouse cornea. Arch. Virol. 140, 1469-1472. 

Marchetti, M., Longhi, C., Conte, M.P., Pisani, S., Valenti, P., and Seganti, L. 1996. Lactoferrin inhibits herpes simplex virus type 1 adsorption to Verop cells. Antiviral Res. 29, 221—231. 

The CAP have been reported to inhibit HIV type 1 (HIV-1) integrase and HIV-1 replications at concentrations as low as 10 p,M (McDougall et al., 1998 King et al., 1999 Reinke et al., 2002). Cichoric acid inhibited 50% of the integrase activity and blocked HIV-1 infections by 50% at concentrations of 0.3 and 4 p,M, respectively (Robinson et al., 1996a,b). Hexane extracts of Echinacea roots were found to have antiviral activity against the Herpes simplex virus type 1 at a 0.12 mg/ml concentration (Binns et al., 2002d). 

Siciliano, R., Rega, B., Marchetti, M., Seganti, L., Antonini, G., and Valenti, P. 1999. Bovine lactoferrin peptidic fractions involved in inhibition of herpes simplex virus type I infection. Biochem. Biophys. Res. Commun. 264, 19—23. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

EC50 values are the concentrations of compound in mg/ml which inhibited by 50% the production of gp 120 of HIV or SIV, or herpes simplex virus type 1 surface antigens. 

The formation of plaques by Herpes simplex virus Type 2 in embryonic fibroblasts was dose-dependently inhibited by a rosemary extract (2-100 pg/ml). The antiviral activity was further tested in four fractions of the ethanol extract and was found in the hexane fraction (Romero et al., 1989). 

Cabral GA, McNerney PJ, Mishkin EM (1987b) Delta-9-tetrahydrocannabinol inhibits the splenocyte proliferative response to herpes simplex virus type 2. Immunopharmacol Immunotoxicol 9 361-370... 

Castanospermine has been screened for efficacy against simian immunodeficiency virus (265), and has been shown to prevent syncytium formation in feline astrocyte cultures infected with the feline immimodeficiency virus by modifying the viral cell envelope (266). It suppressed syncytium formation and hemolytic activity in baby hamster kidney cells infected with Newcastle disease virus however, synthesis and cell surface expression of the hemagglutinin-neuraminidase glycoprotein in the viral envelope were not affected, which strengthens the hypothesis that poor transport of the parent alkaloid across membrane barriers may limit its therapeutic use (267). Both 239 and its 6-0-butanoyl ester had comparable relative toxicities and antiviral effects on Rauscher murine leukemia virus (268), but the ester was more potent than the parent alkaloid in inhibiting replication of Moloney murine leukemia virus (258). The ester was also active against herpes simplex viruses types 1 and 2 (269,270). In the latter case, conclusive evidence was provided for intracellular hydrolysis to 239. 

The herpes simplex virus Type I presents a widely distributed infective profile. HSV-1 enters cells through the fibroblast growth factor receptor (Kaner et al., 1990). There is no viral entry into cells that do not express these receptors and entry of the virus is inhibited by peptide receptor antagonists. 

Solasonine inhibited larval development and pupation in Earias insulana [644], inhibited elongation of letuce seed radicles [646], inhibited the infectivity of herpes simplex virus type 1 and was cytotoxic to Vero cell cultures [652]. Solasonine weakly inhibited mycelium development in the fungus Phoma medicaginis synergism was observed in combination with 290 [647]. Solasonine lysed Penicillium notatum-derived protoplasts and bovine erythrocytes [648] and weakly disrupted stigmasterol and ergosterol liposomes [649] in each case, 290 was considerably more active. The completely assigned H and 13C NMR spectra for 291 have been reported [642],... 

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