Related Experiment Video
Updated: Jul 19, 2026
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
HIV-1 entry inhibitors: classes, applications and factors affecting potency
Jasminka Sterjovski1, Melissa J Churchill, Steve L Wesselingh
1Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
Current HIV Research
|November 1, 2006
Summary
New antiviral drugs, known as entry inhibitors, show promise for treating human immunodeficiency virus type-1 (HIV-1) infection. Understanding HIV-1 envelope protein evolution is key to developing effective entry inhibitors against resistant strains.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Antiviral agents targeting human immunodeficiency virus type-1 (HIV-1) entry are crucial for treatment.
- Viral evolution and drug resistance pose significant challenges in HIV-1 therapy.
- The HIV-1 envelope protein (Env) variability complicates the development of entry inhibitors.
Purpose of the Study:
- To review current and emerging HIV-1 entry inhibitors.
- To examine factors influencing the potency of entry inhibitors.
- To highlight the importance of considering viral evolution in therapeutic design.
Main Methods:
- Review of preclinical and clinical data on HIV-1 entry inhibitors.
- Analysis of the relationship between Env evolution, co-receptor interactions, and fusogenicity.
- Examination of factors affecting inhibitor potency against HIV-1 variants.
Main Results:
- Entry inhibitors targeting attachment, co-receptor engagement, and fusion are promising.
- HIV-1 Env evolution can increase Env-CCR5 interactions, enhancing fusogenicity and reducing inhibitor sensitivity.
- Late-emerging HIV-1 variants present unique challenges for entry inhibitor efficacy.
Conclusions:
- Entry inhibitors represent a vital class of therapeutics for HIV-1 infection.
- Understanding Env variability and its impact on viral entry is critical for designing effective and durable treatments.
- Future HIV-1 therapeutic strategies must account for viral evolution and the properties of emergent strains.
Related Concept Videos
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
01:22Antiviral 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),...
01:10Retrovirus 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...
01:30Inhibitors 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...
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
01:18Factors Affecting Protein-Drug Binding: Drug-Related Factors
Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In contrast,...
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In contrast,...