Antimicrobial Chemotherapy

Because of the nature of viruses as intracellular parasites, very few clinical useful agents to treat virus infections have been produced. Development of drugs that are active against viruses is one of the most challenging areas in antimicrobial chemotherapy.

The purine acyclovir, or acycloguanosine, inhibits the thymidine kinase of herpes viruses. It is particularly active against herpes simplex virus types 1 and 2, is less active against varicella zoster virus and has significantly reduced activity against cytomegalovirus. It has prevented significant mortality associated with herpes simplex encephalitis and is of value in treating varicella zoster infections in immunocompromised patients.

Acyclovir is also used for the treatment of severe cases of genital herpes. Resistance to acyclovir because of mutations in the thymidine kinase gene limits the use of this drug for more trivial conditions. It does not eradicate latent virus but acyclovir does shorten the duration of clinical symptoms. Gancyclovir is an analogue of acyclovir that is active against cytomegalovirus as well as other herpes viruses.

Chemical structure of acyclovir

Chemical structure of gancyclovir

 

This agent is used to treat shingles, particularly in elderly or debilitated patients. It is also used for the treatment of influenza A virus infections. Its mode of action has not been fully elucidated but it is thought to interfere with the uncoating of the virus. During epidemics of influenza A virus infection, it may be used as a prophylactic agent to prevent disease in the most vulnerable patients.

Chemical structure of amantidine

This is a broad-spectrum drug active against both RNA and DNA viruses. In the Developed World, its principal use is in treating severe respiratory syncytial virus infections in infants. The virus infects the bronchioles, causing bronchiolitis and the drug may be inhaled. Its mode of action is unclear.

Chemical structure of ribavirin

This was formerly called azidothymidine and is also known as AZT. It is an anti-retrovirus agent that is phosphorylated to form a triphosphate derivative inside infected and uninfected calls. Zidovudine triphosphate is a competitive inhibitor of the retrovirus reverse transcriptase, the enzyme that produces provirus DNA from the virus RNA template. Its principal use is in the management of patients with advanced human immunodeficiency virus disease (AIDS).

Chemical structure of zidovudine