By Gail Skowron, Richard Ogden
A magisterial survey of all points of the opposite transcriptase inhibitors (RTIs) used to regard HIV/AIDS, together with drug discovery, pharmacology, improvement of drug resistance, toxicity, and prevention of mother-to-child transmission of HIV/AIDS. The authors synthesize our present knowing of the function of opposite transcriptase within the viral existence cycle, describe the invention and improvement of 8 nucleoside and nucleotide analogs that signify milestones in remedy background, and punctiliously speak about the query of toxicity and resistance to this type of gear. additionally they tackle 3 non-nucleoside RTIs and their pharmacokinetics and comparative scientific efficacy, new RTIs presently below improvement, and the influence of licensed brokers on remedy, often, and on vertical transmission within the constructing global.
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Additional resources for Reverse Transcriptase Inhibitors in HIV AIDS Therapy (Infectious Disease)
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Canard B, Sarfati SR, Richardson CC. Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1 reverse transcriptase to the 3′-azido-3′deoxythymidine 5′-monophosphate-terminated primer. J Biol Chem 1998;273(23): 14,596–14,604. 45. Arion D, Kaushik N, McCormick S, Borkow G, Parniak MA. Phenotypic mechanism of HIV-1 resistance to 3′-azido-3′-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase.
Biochemistry 1997;36:3179–3185. 88. Muller WE, Weiler BE, Charubala R, et al. Cordycepin analogues of 2′,5′-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry 1991;30(8):2027–2033. 89. Buiser RG, DeStefano JJ, Mallaber LM, Fay PJ, Bambara RA. Requirements for the catalysis of strand transfer synthesis by retroviral DNA polymerases. J Biol Chem 1991;266(20):13,103–13,109. 90. Morris MC, Robert-Hebmann V, Chaloin L, et al. A new potent HIV-1 reverse transcriptase inhibitor.
There are some exceptions, however, such as PETT-2, which inhibits HIV-2 RT with an IC50 of 2 µM (17). The key aromatic residues of Tyr181 and Tyr188 involved in aromatic ring stacking with many inhibitors are changed to aliphatic side chains in HIV-2 RT (Ile181 and Leu188). 35-Å resolution (84). The overall fold of the unliganded HIV-2 RT is similar to that of the HIV-1 RT, with the thumb domain in a folded-down conformation. Comparison of the apo structures of HIV-1 and HIV-2 RT in the region of the NNRTI site shows differences 24 Stammers and Ren Fig.