Herpes simplex virus type 1

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. 

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

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. 

Miskin EM, Cabral GA. Delta-9-tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in B6C3F mice. J Gen Virol 1985 66 2539-2549. 

Herpes genitalis Herpes simplex virus, types 1 and II... 

The Case Study Herpes Simplex Virus Type 1 Thymidine Kinase Substrates and Inhibitors... 

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. 

Glaser, R. and Kiecolt-Glaser, L, Chronic stress modulates the virus-specific immune response to latent herpes simplex virus type 1, Ann. Behav. Med., 78, 1997. 

Padgett, D.A. et al., Social stress and the reactivation of latent herpes simplex virus type 1, Proc. Nat. Acad. Set, 95, 7231, 1998. 

Cabral, G.A. et al., Effect of delta 9-tetrahydrocannabinol on herpes simplex virus type 2 vaginal infection in the guinea pig, Proc. Soc. Exp. Biol. Med., 182, 181, 1986. 

Cook, R.L. et al., Increased prevalence of herpes simplex virus type 2 among adolescent women with alcohol use disorders, J. Adolesc. Health, 30, 169, 2002. 

Despite the protective effect of NO against various viral infections, workers in several studies have shown a harmful role of NO in many systems. NO seems to play a part in the development of pneumonia caused by influenza virus [128], in the pathogenesis in mice of tick-borne encephalitis flavivirus infection [131], and in worsening the course of the murine myocarditis caused by coxsackievirus B3 [132]. In addition, pneumonia in mice induced by herpes simplex virus type 1 could be suppressed by the inhibitor of iNOS [133]. The issue of whether NO acts as an inhibitor of viral replication or as a harmful agent, therefore, remains unanswered. This issue is particularly evident in HIV-1 infection, since NO seems to act as a double-edged sword in the pathogenesis of HIV-1. 

The 9-alkoxyguanine 998 has potent and selective antiherpes virus activity. The racemic guanine derivative 1003 showed potent and selective activity against herpes simplex virus type 1 and 2, but was less active against varicella zoster virus (VZV). Its antiviral activity is attributable to the S... 

Alkylation of the uracil derivatives with the epoxide 1097 gave 1098, whose hydroxylation gave 1099, which had no significant activity against herpes simplex virus type 1 (94MI6). Uracil derivatives derived from 1068 were also prepared. 

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 Penciclovir is an antiviral agent active against herpes viruses. It has in vitro inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). 

Primary keratoconjunctivitis and recurrent epithelial keratitis caused by herpes simplex virus types 1 and 2. 

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. 

In 1990, Moore et al. reported the isolation of S-cyano-h-methoxy-ll-methyl-indolo[2,3-fl]carbazole (357), along with a minor component, 6-cyano-5-methoxy-indolo[2,3-fl]carbazole (358), from the blue-green alga Nostoc sphaericum EX-5-1 (340). These were the first, naturally occurring, indolo[2,3-fl]carbazole alkaloids with a simple indolo[2,3-fl]carbazole (356) framework (Scheme 2.92). These alkaloids are moderately active against herpes simplex virus type 2 and are weakly cytotoxic against murine and human cancer cell lines (340). 

The tubingensins A (379) and B (380) showed activity against the widespread crop pest Heliothis zea, and display in vitro anti-viral activity against herpes simplex virus type 1 with IC50 values of 8 and 9 pg/mL, respectively (346) (see Scheme 2.100). Some bis-basic ethers of carbazoles are anti-viral. When tested against Encephala myocarditis viral infection, several N-ethyl substituted bis-basic carbazoles of the general formula 490 were shown to be active (448) (Scheme 4.9). 

Aoki, H., T. Akaike, K. Abe, et al. Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against Herpes Simplex Virus Type I in vitro and in vivo. Antimicrob Agents Chemother 1995 39(4) 846-849. 

Nagasaka, K., M. Kurokawa, M. Imakita, K. Terasawa, and K. Shiraki. Efficacy of kakkon-to, a traditional herb medicine, in herpes simplex virus type 1 infection in mice. J Med Virol 1995 46(1) 28-34. 

Viral DNA polymerase is an important catalyst for the synthesis of viral nucleic acids. DNA polymerase inhibitors have already been encountered as antitumor agents. Ara-A (9.5, vidarabine) is a DNA polymerase inhibitor that has demonstrated activity against herpes simplex virus type I (HSV-1) infections, responsible for cold sores on... 

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