ArticleRetrovirology2013
Functional conservation of HIV-1 Gag: implications for rational drug design.
Article in Retrovirology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Trial
- Capsid-Targeting Biologic Achieves Broad HIV-1 Neutralization with a High Barrier to Resistance.International journal of molecular sciences · 2026Article
- Changing selection on amino acid substitutions in Gag protein between major HIV-1 subtypes.Virus evolution · 2024Article
- In-house ELISA protocols for capsid p24 detection of diverse HIV isolates.Virology journal · 2023Article
- Antiviral Properties of HIV-1 Capsid Inhibitor GSK878.Antimicrobial agents and chemotherapy · 2023Article
- HIV-1 Group M Capsid Amino Acid Variability: Implications for Sequence Quality Control of Genotypic Resistance Testing.Viruses · 2023Article
- Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication.International journal of molecular sciences · 2023Article
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- The HIV-1 Gag Protein Displays Extensive Functional and Structural Roles in Virus Replication and Infectivity.International journal of molecular sciences · 2022Review
- Uracil derivatives as HIV-1 capsid protein inhibitors: design,RSC advances · 2022Article
- Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV.BMC infectious diseases · 2022Article
- Specific Interaction of DARPin with HIV-1 CAViruses · 2022Article
- Genetic Diversity and Low Therapeutic Impact of Variant-Specific Markers in HIV-1 Pol Proteins.Frontiers in microbiology · 2022Article
- HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir.Frontiers in microbiology · 2022Article
- Rotten to the core: antivirals targeting the HIV-1 capsid core.Retrovirology · 2021Review
- HIV Capsid Inhibitors Beyond PF74.Diseases (Basel, Switzerland) · 2019Review
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation.Journal of the American Chemical Society · 2019Article
- CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHIV-1 replication can be successfully blocked by targeting gag gene products, offering a promising strategy for new drug classes that complement current HIV-1 treatment options. However, naturally occurring polymorphisms at drug binding sites can severely compromise HIV-1 susceptibility to gag inhibitors in clinical and experimental studies. Therefore, a comprehensive understanding of gag natural diversity is needed.
findingsWe analyzed the degree of functional conservation in 10862 full-length gag sequences across 8 major HIV-1 subtypes and identified the impact of natural variation on known drug binding positions targeted by more than 20 gag inhibitors published to date. Complete conservation across all subtypes was detected in 147 (29%) out of 500 gag positions, with the highest level of conservation observed in capsid protein. Almost half (41%) of the 136 known drug binding positions were completely conserved, but all inhibitors were confronted with naturally occurring polymorphisms in their binding sites, some of which correlated with HIV-1 subtype. Integration of sequence and structural information revealed one drug binding pocket with minimal genetic variability, which is situated at the N-terminal domain of the capsid protein.
conclusionsThis first large-scale analysis of full-length HIV-1 gag provided a detailed mapping of natural diversity across major subtypes and highlighted the considerable variation in current drug binding sites. Our results contribute to the optimization of gag inhibitors in rational drug design, given that drug binding sites should ideally be conserved across all HIV-1 subtypes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.