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Retrovirus Life Cycles01:10

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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Updated: Sep 4, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

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Approved HIV reverse transcriptase inhibitors in the past decade.

Guangdi Li1, Yali Wang1, Erik De Clercq2

  • 1Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China.

Acta Pharmaceutica Sinica. B
|July 18, 2022
PubMed
Summary

This review covers recent HIV reverse transcriptase inhibitors, crucial for HIV treatment and prevention. It details their discovery, effects, and clinical success, highlighting future drug development needs.

Keywords:
3TC, (−)-2′,3′-dideoxy-3′-thiacytidine (common name, lamivudine)ABC, abacavirATV, atazanavirAZT, 3′-azido-3′-deoxy-thymidine (common name, zidovudine)BIC, bictegravirCAB, cabotegravirCC50, the 50% cytotoxic concentrationCOBI, cobicistatClinical efficacyDOR, doravirineDPV, dapivirineDRV, darunavirDTG, dolutegravirEACS, European AIDS Clinical SocietyEC50, half maximal effective concentrationEFV, efavirenzESV, elsulfavirineEVG, elvitegravirF, bioavailabilityFDA, US Food and Drug AdministrationFTC, (−)-2′,3′-dideoxy-5-fluoro-3′-thiacytidine (common name, emtricitabine)HAARTHAART, highly active antiretroviral therapyHIV treatmentHIV, human immunodeficiency virusIAS-USA, International Antiviral Society-USAIC50, half maximal inhibitory concentrationMSM, men who have sex with menNNRTINNRTI, non-nucleoside reverse transcriptase inhibitorNRTINRTI, nucleoside/nucleotide reverse transcriptase inhibitorRPV, rilpivirineTAF, tenofovir alafenamideTDF, tenofovir disoproxil fumaratet1/2, elimination half-life

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Area of Science:

  • Virology
  • Pharmacology
  • Drug Discovery

Background:

  • HIV reverse transcriptase (RT) inhibitors are vital for highly active antiretroviral therapies (HAARTs) and pre-exposure prophylaxis.
  • A comprehensive review of RT inhibitors approved in the last decade, covering their discovery, pharmacology, and clinical efficacy, is currently lacking.

Purpose of the Study:

  • To provide a comprehensive review of HIV reverse transcriptase inhibitors approved in the past decade.
  • To discuss their drug discovery, pharmacology, and clinical efficacy based on randomized controlled trials.
  • To highlight novel RT inhibitors and future directions in antiretroviral drug development.

Main Methods:

  • Comprehensive literature review of HIV reverse transcriptase inhibitors approved in the last ten years.
  • Analysis of drug discovery pathways, pharmacological profiles, and clinical efficacy data from randomized controlled trials.
  • Identification and discussion of novel investigational RT inhibitors.

Main Results:

  • Detailed review of approved RT inhibitors including tenofovir alafenamide, rilpivirine, doravirine, dapivirine, azvudine, and elsulfavirine.
  • Summary of their drug discovery, pharmacology, and clinical efficacy in randomized controlled trials.
  • Highlighting of novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150.

Conclusions:

  • Recent advancements in HIV reverse transcriptase inhibitors have significantly impacted HIV treatment and prevention.
  • Future research should focus on developing next-generation inhibitors with improved pharmacokinetic properties and activity against drug-resistant strains.
  • Continued innovation in antiretroviral therapy is essential for combating the evolving HIV epidemic.