Proteins and Disease | Structural Basis of HIV Reverse Transcription, Inhibition, and Drug Resistance

Cilento, Maria E.; Kirby, Karen A.; Tedbury, Philip R.; Sarafianos, Stefan G.

doi:10.1016/b978-0-12-809633-8.21570-7

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2021

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“…Strand displacement activity of RT to the PBS and PPT ends and/or DNA repair and ligation lead to dsDNA or a circular intermediate with two long terminal repeats (LTRs). Figure adapted with permission from ref . Copyright 2020 Elsevier.…”

Section: Introductionmentioning

confidence: 99%

Avoiding Drug Resistance in HIV Reverse Transcriptase

2021

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HIV reverse transcriptase (RT) is an enzyme that plays a major role in the replication cycle of HIV and has been a key target of anti-HIV drug development efforts. Because of the high genetic diversity of the virus, mutations in RT can impart resistance to various RT inhibitors. As the prevalence of drug resistance mutations is on the rise, it is necessary to design strategies that will lead to drugs less susceptible to resistance. Here we provide an in-depth review of HIV reverse transcriptase, current RT inhibitors, novel RT inhibitors, and mechanisms of drug resistance. We also present novel strategies that can be useful to overcome RT’s ability to escape therapies through drug resistance. While resistance may not be completely avoidable, designing drugs based on the strategies and principles discussed in this review could decrease the prevalence of drug resistance.

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Section: Introductionmentioning

confidence: 99%