9NLP
HIV-1 Reverse Transcriptase with New Non-Nucleoside Reverse Transcriptase Inhibitor 12126065
This is a non-PDB format compatible entry.
Summary for 9NLP
| Entry DOI | 10.2210/pdb9nlp/pdb |
| EMDB information | 49521 |
| Descriptor | Reverse transcriptase p66 subunit, Reverse transcriptase p51 subunit, 4-({5-amino-1-[6-(2-cyanoethyl)naphthalene-1-sulfonyl]-1H-1,2,4-triazol-3-yl}amino)-2-chlorobenzonitrile (3 entities in total) |
| Functional Keywords | reverse transcriptase, viral protein |
| Biological source | HIV-1 06TG.HT008 More |
| Total number of polymer chains | 2 |
| Total formula weight | 117827.66 |
| Authors | Young, M.A.,Lane, T.R.,Raman, R.,Nelson, J.A.E.,Riabova, O.,Kazakova, E.,Monakhova, N.,Tsedilin, A.,Rees, S.D.,Quinnell, D.,Chang, G.,Ekins, S. (deposition date: 2025-03-03, release date: 2025-05-07, Last modification date: 2025-05-21) |
| Primary citation | Young, M.A.,Lane, T.R.,Raman, R.,Nelson, J.A.E.,Riabova, O.,Kazakova, E.,Monakhova, N.,Tsedilin, A.,Rees, S.D.,Quinnell, D.,Makarov, V.,Chang, G.,Ekins, S. Cryo-EM Structure of HIV-1 Reverse Transcriptase with N -Phenyl-1-(phenylsulfonyl)-1 H -1,2,4-triazol-3-amine: A New HIV-1 Non-nucleoside Inhibitor. Acs Infect Dis., 11:1257-1267, 2025 Cited by PubMed Abstract: The use of highly active antiretroviral therapy (HAART) has made the human immunodeficiency virus (HIV) a chronic disease rather than a terminal disease. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of HAART, although we are seeing clinically relevant drug-resistant mutants such that there is a need to develop new molecules. We recently identified a new class of -phenyl-1-(phenylsulfonyl)-1-1,2,4-triazol-3-amine HIV-1 NNRTI, with one known as compound 12126065, with sub nanomolar (nM) potency in TZM-bl cells (HeLa cells expressing CD4, CCR5, and CXCR4) with no in vivo acute or subacute toxicity. We now describe the cryo-EM structure of this molecule (resolution of 3.53 Å) and compare it to analogues and other known NNRTIs. We also describe the synthesis and activity of five additional analogues of this class of compounds, some of which have promising activity against a K103N/Y181C (A17) double mutant, which will enable the design of future molecules. PubMed: 40304150DOI: 10.1021/acsinfecdis.5c00189 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.53 Å) |
Structure validation
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