ArticleAntimicrobial agents and chemotherapy2012
HIV gp120 H375 is unique to HIV-1 subtype CRF01_AE and confers strong resistance to the entry inhibitor BMS-599793, a candidate microbicide drug.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- A gp41 HR2 residue modulates the susceptibility of HIV-1 envelope glycoproteins to small molecule inhibitors targeting gp120.Journal of virology · 2025Article
- Structure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir.Nature communications · 2023Article
- To prescreen or not to prescreen for broadly neutralizing antibody sensitivity in HIV cure-related trials.Journal of virus eradication · 2023Article
- Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120.Cell chemical biology · 2023Article
- Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.Journal of virology · 2023Article
- The Genesis and Future Prospects of Small Molecule HIV-1 Attachment Inhibitors.Advances in experimental medicine and biology · 2022Review
- Small Molecule HIV-1 Attachment Inhibitors: Discovery, Mode of Action and Structural Basis of Inhibition.Viruses · 2021Review
- Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay.The Journal of antimicrobial chemotherapy · 2021Article
- Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Review
- Article
- Article
- Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529.Nature chemical biology · 2017Article
- Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses.Journal of virology · 2017Article
- CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.Scientific reports · 2016Article
- Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor.Bioorganic & medicinal chemistry · 2015Article
- Peptide Triazole Inactivators of HIV-1 Utilize a Conserved Two-Cavity Binding Site at the Junction of the Inner and Outer Domains of Env gp120.Journal of medicinal chemistry · 2015Article
- A broad HIV-1 inhibitor blocks envelope glycoprotein transitions critical for entry.Nature chemical biology · 2014Article
- Binding mode characterization of NBD series CD4-mimetic HIV-1 entry inhibitors by X-ray structure and resistance study.Antimicrobial agents and chemotherapy · 2014Article
- Detailed study of the interaction between human herpesvirus 6B glycoprotein complex and its cellular receptor, human CD134.Journal of virology · 2014Article
- Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibitors.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ∼3 ρM and 7 μM at 50% effective concentrations (EC(50)s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, and in silico drug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.