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Related Concept Videos

Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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 retrovirus to...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Drugs Affecting GI Tract Motility: Antimicrobials as Antidiarrheal Agents01:18

Drugs Affecting GI Tract Motility: Antimicrobials as Antidiarrheal Agents

Acute diarrhea, a common gastrointestinal disturbance, is characterized by the rapid evacuation of fluid stools, leading to an excessive weight in fluid. This condition typically arises from disorders affecting intestinal water and electrolyte transport. It can be triggered by an increased osmotic load within the intestine, excessive secretion of electrolytes and water, mucosal exudation of protein and fluid, or altered intestinal motility. The primary risks of acute diarrhea are dehydration...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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Related Experiment Video

Updated: Jun 25, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

Reverse transcriptase inhibitors as potential colorectal microbicides.

Carolina Herrera1, Martin Cranage, Ian McGowan

  • 1Division of Cellular and Molecular Medicine, St George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.

Antimicrobial Agents and Chemotherapy
|March 5, 2009
PubMed
Summary
This summary is machine-generated.

Combination therapy with reverse transcriptase inhibitors (RTIs) effectively inhibits HIV-1 infection in colorectal tissue. Dual RTI combinations, including nucleoside (NRTI) and non-nucleoside (NNRTI) types, are crucial for combating resistant HIV strains.

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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

Published on: May 9, 2025

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Last Updated: Jun 25, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

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

Published on: May 9, 2025

Area of Science:

  • Virology
  • Immunology
  • Pharmacology

Background:

  • Developing effective rectal microbicides is crucial for preventing HIV-1 transmission.
  • Reverse transcriptase inhibitors (RTIs) are key antiretroviral agents.
  • Understanding drug resistance and mucosal fitness is vital for microbicide design.

Purpose of the Study:

  • To evaluate the efficacy of combining different reverse transcriptase inhibitors (RTIs) against HIV-1 infection in colorectal tissue ex vivo.
  • To assess the potential of combination RTI therapy as a rectal microbicide strategy.
  • To investigate the impact of RT mutations on HIV-1 replication in colorectal explants.

Main Methods:

  • Ex vivo culture of human colorectal explants.
  • Inhibition assays using TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants.
  • Evaluation of nucleoside RTI (NRTI) PMPA (tenofovir) and non-nucleoside RTIs (NNRTIs) UC-781 and TMC120 (dapivirine).
  • Testing of single compounds and dual combinations (NRTI-NNRTI, NNRTI-NNRTI).

Main Results:

  • Individual RTIs inhibited HIV-1 replication in cellular and tissue models.
  • Dual RTI combinations demonstrated superior efficacy compared to single agents.
  • Combination therapy was effective against both NRTI- and NNRTI-resistant HIV-1 isolates.
  • Single point mutations in RT affecting RTI resistance impacted HIV-1 replication capacity in colorectal explants.

Conclusions:

  • Colorectal explants serve as a valuable model for screening combination microbicides.
  • The study highlights the importance of combination therapy for overcoming RTI resistance.
  • Findings support the rational design of effective rectal microbicides incorporating combination RTI strategies.