Viruses Simplex

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). 

Acute infection with Hetpes simplex viruses (HSV) results in painful rashes on skin and mucous membranes. HSV-1 mainly causes cold sores around the mouth (hetpes labialis) or eyes (keratitis), whereas infection by HSV-2 mostly results in sores in the genital or anal area. Less frequently, HSV also causes severe infections in newborns or potentially fatal encephalitis. HSV remains latent and can be reactivated by stress, suppression of the immune system or other infections. 

HSV2 (herpes simplex virus 2), which causes significant morbidity and is an important cofactor for the transmission of HIV infection was recently targeted in a mouse model by local application of siRNA mixed with lipids. The results suggested that siRNA could work as active components of microbicides to prevent viral infection or transmission [2]. 

Lemon balm isa perennial herb with heart-shaped leaves that has been used for hundreds of years. Its scientific name is Melissa officinalis. Traditionally the herb has been used for Graves disease (see Chap. 51), asa sedative, arrtispasmodic, and an antiviral agent. When used topically, lemon balm has antiviral activity against herpes simplex virus(HSM). No adverse reactions have been reported when lemon balm is used topically. 

Initial and recurrent mucosal and cutaneous herpes simplex virus (HSV) 1 and 2 infections in... 

Acyclovir (Zovirax) and penciclovir (Denavir) are the only topical antiviral dragp currently available These dragp inhibit viral replication. Acyclovir is used in the treatment of initial episodes of genital herpes, as well as heqies simplex virus infections in immunocompromised patients (patients with an immune system incapable of fighting infection). Penciclovir is used for the treatment of recurrent herpes labialis (cold sores) in adults. 

La, T.N.B. Latchman, D.S. (1988). A cellular protein related to heat shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells. Exp. Cell Res. 178, 169-179. 

Crute JJ, Grygon CA, Hargrave KD, Simoneau B, Faucher AM, Bolger G, Kibler P, Liuzzi M, Cordingley MG (2002) Herpes simplex virus heUcase-primase inhibitors are active in animal models of human disease, Nat Med 8 386-391... 

Sheaffer AK, Newcomb WW, Gao M, Yu D, Weller SK, Brown JC, Tenney DJ (2001) Herpes simplex virus DNA cleavage and packaging proteins associate with the procapsid prior to its maturation. J Virol 75 687-698... 

Pelham, H.R.B. Bienz, M. (1982). A synthetic heat-shock promoter element confers heat-inducibility on the herpes simplex virus thymidine kinase gene. EM BO Journal, 1,1473-7. 

Flistory of recurrent herpes simplex virus infection... 

Figure 37-7. Transcription elements and binding factors in the herpes simplex virus thymidine kinase ffW gene. DNA-dependent RNA polymerase II binds to the region of the TATA box (which is bound by transcription factor TEND) to form a multicomponent preinitiation complex capable of initiating transcription at a single nucleotide (+1).The frequency of this event is increased by the presence of upstream c/s-acting elements (the GC and CAAT boxes). These elements bind frans-acting transcription factors, in this example Spl and CTF (also called C/EBP, NF1, NFY). These cis elements can function independently of orientation (arrows).

Miguelez M, Correa-Nazco VJ et al (1999) [Lumbosacral polyradiculomyelitis caused by herpes simplex virus (HSV) in a patient with AIDS]. An Med Interna 16(8) 417 19 MiUer RJ, Meucci O (1999) AIDS and the brain is there a chemokine connection Trends Neurosd 22(10) 471-479... 

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. 

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. 

The genes of the inducible and the constitutively expressed forms of NOS have been cloned and expressed. The expression of inducible NOS in the brain tissue of animals with experimentally induced neurological disorders (boma disease virus and rabies virus in rats), herpes simplex virus (mice) and experimental allergic encephalitis (in rats) suggests that NO produced by induced NOS may be a toxic fector in the pathogenesis of neurological diseases (Koprowski et /., 1993). 

Cenital herpes simplex virus. Characterized by vesicular or ulcerative lesions. Diagnosis confirmed by virologic or serologic testing. Prodrome manifests as pain, burning, or itching at the site where lesions will develop. 

Spectinomycin (Trobicin) Herpes Simplex Virus 2 g intramuscularly once Second-line agent in pregnancy for cephalosporin-allergic patients... 

Herpes simplex virus may be transmitted to the neonate if active vaginal lesions or the prodrome is present at the time of birth. Consequently, cesarean section often is recommended for these women. Vaginal delivery is indicated if vaginal lesions or the prodrome are not present. 

Genital herpes simplex virus. Infants born to mothers with active disease at birth should be monitored for signs and symptoms of disease. Surveillance culture of mucosal surfaces is optional.38... 

Reactivation of Latent Disease - Herpes Simplex Virus, Tuberculosis... 

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