Herpes simplex

Herpes Simplex. There are two types of herpes simplex vims (HSV) that infect humans. Type I causes orofacial lesions and 30% of the U.S. population suffers from recurrent episodes. Type II is responsible for genital disease and anywhere from 3 x 3 x 10 cases per year (including recurrent infections) occur. The primary source of neonatal herpes infections, which are severe and often fatal, is the mother infected with type II. In addition, there is evidence to suggest that cervical carcinoma may be associated with HSV-II infection (78—80). 

BVdU differs from IdU and F TdU by being specifically phosphorylated in the 5 -position by herpes simplex vims type-1 (HSV-1) induced thymidine kinase. This restricts its action to cells infected by HSV-1. It is less active against genital herpes (HSV-2). HSV-l-induced thymidine kinase converts BVdU to the corresponding 5 -mono- and diphosphate, but HSV-2-induced thymidine kinase stops at the stage of the 5 -phosphate of BVdU. Apparendy, cellular kinases phosphorylate BVdU-5 -diphosphate to the corresponding 5 -triphosphate, which inhibits HSV-1 DNA polymerase to a greater extent than similar cellular DNA polymerases. 

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

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). 

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]. 

Palliser D, Chowdhury D, Wang QY et al (2006) An siRNA-based microbicide protects mice from lethal herpes simplex vims 2 infection. Nature 439(7072) 89-94... 

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... 

Antiviral drugp interfere with viral reproduction by altering DNA synthesis. These drug are used in the treatment of herpes simplex infections of the eye, treatment in immunocompromised patients with cytomegalovirus (CMV) retinitis, and for the prevention of CMV retinitis in patients undergoing transplant. 

These drug are contraindicated in individuals with known hypersensitivity to an individual drug or any components of the drug. The NSA.ID flurbiprofen is contraindicated in patients with herpes simplex keratitis. Diclofenac and ketorolac are contraindicated in patients who wear soft contact lenses (may cause ocular irritation). 

The antibiotic and sulfonamide ophthalmics are contraindicated in patients with a hypersensitivity to the drug or any component of the drug. These dru are also contraindicated in patients with epithelial herpes simplex keratitis, varicella, mycobacterial infection of the eye, and fungal diseases of the eye There are no significant precautions or interactions when the dru are administered as directed by the primary health care provider. 

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. 

ATC D06BB01 J05AB02 SOlADOl Use chemotherapeutic (Herpes simplex)... 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

Al-Kobaisi MF, Rixon FJ, McDougaU I, Preston VG (1991) The herpes simplex vims UL33 gene product is required for the assembly of fiiU capsids. Virology 180 380-388 Anthony NJ (2004) HlV-1 integrase a target for new AIDS chemotherapeutics. Curr Top Med... 

Beard PM, Duffy C, Baines JD (2004) Quantification of the DNA cleavage and packaging proteins UL15 and UL28 in A and B capsids of herpes simplex vims type 1. J Virol 78 1367-1374 Betz UA, Fischer R, Kleymann G, Hendrix M, Rubsamen-Waigmann H (2002) Potent in vivo antiviral activity of the herpes simplex vims primase-helicase inhibitor BAY 57-1293. Antimicrob Agents Chemother 46 1766-1772... 

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