Targets for antiviral therapy of human immunodeficiency virus infection.
The development of potent anti-retroviral drugs is central to the control of human immunodeficiency virus (HIV) infection and the prevention of disease. Despite the benefit (albeit limited) shown by the early trials of zidovudine in patients with acquired immune deficiency syndrome (AIDS), there is general agreement that the best prospects for therapeutic intervention lie in the use of agents early in the infectious process. There is a definite possibility that this can be achieved if compounds acting specifically against virus encoded events can be found or developed. Although relatively simple in its structure, HIV is highly sophisticated in its mode of replication. The unique nature of the replication cycle of the retroviridae and the specific controlling mechanisms operative in HIV offer a number of possible targets for chemotherapeutic agents. The details of the structure and replication cycle of HIV will be briefly reviewed with comments on the possible virus specific and non-specific sites for potential antiviral drug development. The first specific target to be recognised was the unique, virus-associated enzyme, the reverse transcriptase (RNA directed DNA polymerase). Several inhibitors of reverse transcriptase were identified during the 1970s (e.g. suramin, HPA23, phosphonoformate). These have been found, in early trials, to be either insufficiently potent or too toxic to consider for development as anti-retroviral drugs. Indeed, knowledge of the pathogenesis of HIV infection led to the realisation that any putative drug would need to satisfy several important criteria; namely potency, low toxicity, easy administration, penetration of the blood-brain barrier and hopefully, low production costs.(ABSTRACT TRUNCATED AT 250 WORDS)
Jeffries
D J
DJ
Department of Virology, St Mary's Hospital Medical School, Paddington, London, U.K.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000517:prevention & control; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005809:Genes, Regulator / Q000187:drug effects; D006678:HIV / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016047:Zalcitabine