Antiviral agent zidovudine

Since 3 -azido-3 -deoxythymidine (AZT, Zidovudine, Retrovir) was identified by Mitsuya and co-workers as a potent antiviral agent against immunodeficiency virus type I (HIV-1), a number of other nucleosides have been found to inhibit HIV-I in vitro. The most important representatives are the 2, 3 -didcoxy nucleosides ddl, ddG, and ddA as well as their corresponding 2, 3 -didehydro derivatives. ... 

MRP4 (ABCC4) mRNA has been detected in the kidney, at the brush-border membrane of proximal tubular cells. It enhances cell resistance to some antiviral agents such as adefovir and zidovudine. It also seems to play an important role in antiviral drugs renal excretion. MRP4 is also the transporter for cyclic AMP and GMP through an ATP-dependent system and it constitutes the elective excretion pathway for cyclic nucleotides in renal epithelial cells. 

The sites at which anti-HIV drugs may. in principle, act, are dealt with in detail under a main heading (see ANTIVIRAL agents). In summary, currently, of the drugs actually in use, a number are reverse transcriptase (enzyme) inhibitors (RTIs). Examples of nucleoside RTIs include zidovudine, didanosine and zalcitabine. Some non-nucleoside RTIs include foscarnet sodium, nevirapine, carbovir and TIBO analogues (some of these are at trial stage only). 

Larder, B. A., Chesebro, B., and Richman, D. D. (1990) Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay. Antimicrob. Agents Chemother. 34,436 141. 

Brody SR, Aweeka FT. Pharmacokinetics of intracellular zidovudine and its phosphorylated anabolites in the absence and presence of other antiviral agents using an in vitro human PBMC model. Clin Pharmacol Ther (1997) 61,149. 

Development of effective antiviral agents has been slow, as the drugs must be highly selective because viral replication depends largely on the metabolic processes ongoing in the invaded cell. Zidovudine is the most important agent available for the treatment of AIDS, and Acyclovir is effective for the treatment of herpes simplex virus infections. 

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