Antiviral drugs herpes viruses

Aciclovir (acyclovir) was one of the first effective selective antiviral agents. It is a guanine derivative of value in treating herpes viruses, though it does not eradicate them, and is only useful if drug treatment is started at the onset of infection. 

A wide variety of organotin compounds developed by Carraher, Sabir, Roner, and others based on known antiviral drugs such as acyclovir and known antibacterial agents such as ciprofloxacin, norfloxacin, cephalexin (structure 11.21), and ampicillin inhibit a wide variety of viruses including ones responsible for many of the common colds, chicken pox, small pox, shingles, and herpes simplex. 

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... 

Trifluridine (5-trifluoromethyl-2 -deoxyuridine) (Viroptic ) is marketed for the topical treatment of herpes simplex virus infection in the eyes. This antiviral drug is a mechanism-based inactivator of thymidylate synthase. The mechanism of inhibition and synthesis of trifluoridine are reported in Chapter 7. 

An unusual feature of the herpes viruses is their preference for nerve cells. Stress to the nervous system, such as emotional stress or sunburn, can cause the virus to replicate, which leads to an outbreak through the skin. When they are not replicating, these viruses remain in nerve cells where they are not detected by the body s immune system, which has little activity in nerve cells. While remaining dormant in the nervous system, the viruses evade not only the immune system but antiviral drugs as well. 

Most bacterial infections can be treated successfully with antibiotics, but the development of satisfactory antiviral agents has been slow. Yet we are susceptible to many dangerous virus diseases, and viruses also take a huge toll among domestic animals and plants.3 The first antiviral drug, 5-iodo-2 -deoxyuridine (idoxuridine), was introduced in 1962 and was used for 20 years by ophthalmologists to treat serious eye infections by the herpes simplex virus (HSV). 

Antiviral Efficacy and Clinical Use. Docosanol (Abreva) is applied topically to treat blisters and cold sores caused by herpes virus simplex.42 This drug is available as an over-the-counter product, and is used primarily to treat recurrent outbreaks of orofacial herpes lesions. 

Other notable research by Elion led to the development of the antiviral drug Acyclovir (acycloguanosine), which has been used to treat the herpes simplex viruses. Her studies during the 1970s showed that Acyclovir inhibited viral replication by interfering with viral DNA synthesis. The sub-... 

Scholar EM, Pratt WB (2000) Chemodrerapy of viral infecdons, I drugs used to treat influenza virus infecdons, herpes virus infecdons, and drugs widr broad-spectrum antiviral acdvity. hr The Andmicrobial Drugs, pp 491—549. Oxford Oxford University Press. 

Famciclovir is an oral prodrug of penciclovir, a selective antiviral drug with activity against Varicella zoster virus. Herpes simplex virus types 1 and 2, and Epstein-Barr virus, as well as human hepatitis B virus. 

Useful antiviral properties were shown by 2-amino-9-(2-hydroxy-ethoxy)methyl-8-azapurin-6-one, the azapurine analog of the purine antiviral drug acyclovir, which is much used in treating human herpes. 9-(2-Hydroxy-4-hydroxymethylcyclopentyl)-8-azaadenine and -hypoxanthine were found to be potent inhibitors of herpes simplex virus (type 1 only) in vitro. 

Ocular antiviral chemotherapy in the horse is adapted from that used in herpes simplex virus (HSV) and varicella zoster keratitis in humans. The agents used are nucleotide analogs capable of inhibiting viral replication by competitive inhibition of the uptake of the nucleotide into the viral genome. These agents are virustatic and require an intact immune system to suppress or eliminate the virus from the eye. They probably do not eradicate any latent infection. The antiviral drugs available currently do not penetrate intact comeal epithelium and are poorly disseminated within the comeal stroma. The availability of these dmgs will vary in different countries and some may only be obtained from hospital pharmacies. 

In the area of classical antimetabolites, a host of highly active new nucleosides have been found that show promise in the chemotherapy of cancer and viral diseases. Classical antimetabolites appear to have a virtual monopoly in the field of antiviral agents. After the discovery of the first effective drugs against,the Herpes virus 28b, c 25), a new breakthrough may have been... 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

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