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- W1744409238 abstract "This chapter discusses the current clinically used reverse transcriptase (RT) inhibitors and some promising new inhibitors still in preclinical development, emphasizing the mechanisms of action of RT inhibitors and the mechanisms of viral resistance that develop upon continued exposure of the virus to these compounds. Once integrated, proviral DNA is therapeutically indistinguishable from cellular DNA and results in persistent HIV infection and the establishment of chronically infected cells that are major contributors to the continued spread of HIV infection in an infected individual. Conversion of HIV genomic RNA into double-stranded viral DNA is a complex process. All chemical steps are catalyzed by the viral enzyme, RT. Because there is no cellular homolog of retroviral RT, the enzyme is an attractive target for the development of HIV therapeutics. Several nucleoside reverse transcriptase inhibitors (Nucleoside RT inhibitors (NRTI)) are in current clinical use. NRTIs are analogs of natural deoxynucleosides, there is the potential that they will be used by normal cellular DNA polymerases, with accompanying toxicity. Thus, the selectivity of NRTI used by HIV-1 RT, compared to that by cellular DNA polymerases, is an important issue in the development of NRTI as therapeutic agents. While many inhibitors of HIV-1 RT DNA polymerase activity have been developed, very few inhibitors of HIV-1 RT ribonuclease H have been described in the chapter. The gene for HIV-1 RT encodes a 66-kDa polypeptide; however, the presumed biologically relevant from of HIV-1 RT is a heterodimer consisting of two subunits of 66 and 51 kDa." @default.
- W1744409238 created "2016-06-24" @default.
- W1744409238 creator A5044933366 @default.
- W1744409238 creator A5046130939 @default.
- W1744409238 date "2000-01-01" @default.
- W1744409238 modified "2023-09-27" @default.
- W1744409238 title "Inhibitors of HIV- I reverse transcriptase" @default.
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