Chemotherapy antiviral drugs

The antiviral strategies discussed earlier as well as all antiviral drugs available to date are based on the principles of conventional chemotherapy. However, recent discoveries and developments in molecular biology have opened perspectives for alternative approaches of intervention. 

The identification of inhibitors of virus subunit assembly has been an objective of virologists for several years but it is only recently that papers have been published that demonstrate the validity of this approach to antiviral chemotherapy. It is hoped that the information provided by the compounds described above will provide the foundation for the generation of potent antiviral drugs to combat diseases caused by HIV, HBV and other viruses. 

In the case of antibiotic chemotherapy, the ideal pharmacodynamic response is usually no pharmacodynamic response the pharmacological target is not normal human cells but rather a parasite, a virus-infected human cell, or a cancerous cell. The less selective the chemotherapeutic drug, the greater the severity of adverse effects. Cancer chemotherapy is often severely toxic, even life threatening. Suppression of a viral infection, such as occurs in the treatment of HIV with antiviral drugs, is often complicated by serious drug-associated toxicity, such as hepatotoxicity or bone marrow suppression. 

PI Becker, Y., Antiviral Drugs Mode of Action and Chemotherapy of Viral Infections of Man, Karger Basel, (1976) p 144. 

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. 

Finally, some viruses have developed resistance to antiviral drugs. HIV chemotherapy now involves... 

Which antiviral drugs work or how the disease is dealt with in terms of public health measures, depends, in part, on the type of virus. The DNA viruses are relatively stable in form since mutations are internally corrected, and here it is often more effective to use vaccination than chemotherapy. By these means smallpox has been eradicated. For some RNA viruses, vaccination is also effective, including poliomyelitis, rubella, measles and mumps, and some rabies strains. Other viruses mutate so rapidly that vaccination is more difTicult, e.g. influenza, the common cold, HIV. 

Borst, P., Balzarini, J., Ono, N., Reid, G., de Vries, H., Wielinga, P., Wijnholds, J., and Zelcer, N. (2004) The potential impact of drug transporters on nucleoside-analog-based antiviral chemotherapy. Antiviral Research, 62 (1), 1-7. 

For the present, perhaps the term "chemotherapy" should be replaced by "antiviral." Few seem clear in their use of the term "chemotherapy" in viral disease. Indeed, in that some of the most interesting antiviral drugs are protective only, the term "chemotherapy" is completely inaccurate. 

As is often the problem with antiviral (and anticancer) chemotherapy, the drugs also inhibit the normal function of essential human enzymes and are very toxic. But biologists discovered an alternative point of attack. An enzyme unique to the virus cuts up long proteins into small pieces essential for the formation of new HIV particles. If this enzyme could be inhibited, no new viruses would be formed and neither should the inhibitor interfere with human biochemistry. 

D. Lembo, R. CavaUi, Nanoparticulate dehvery systems for antiviral drugs. Antiviral Chemistry and Chemotherapy 21 (2010) 53-70. 

Smee, D.F., von Itzstein, M Bhatt, B and Tarbet, E.B. (2012) Exacerbation of influenza virus infections in mice by intranasal treatments and implications for evaluation of antiviral drugs. Antimicrobial Agents and Chemotherapy,... 

For more on the sequence of virus invasion of the host cell and reproduction there, and for chemotherapy with the new antiviral drugs, see Section 6.3b. For further reading on viruses, see Fenner et aL 1974. 

Ilyushina NA, Bovin NV, Webster RG, Govorkova EA (2006) Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70 121-131... 

Research in antiviral chemotherapy began in the early 1950s, when the search for anticancer drugs generated several new compounds capable of inhibiting viral DNA synthesis. The two first-generation antivirals, 5-iododeoxyuridine and trifluorothymidine, had poor specificity (ie, they inhibited host cellular as well as viral DNA) that rendered them too toxic for systemic use. However, both are effective when used topically for the treatment of herpes keratitis. 

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