8VQL
Crystal structure of the A/Puerto Rico/8/1934 (H1N1) influenza virus hemagglutinin in complex with small molecule 6S prime
This is a non-PDB format compatible entry.
Summary for 8VQL
| Entry DOI | 10.2210/pdb8vql/pdb |
| Descriptor | Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | h1n1, antibody, hemagglutinin, viral protein |
| Biological source | Influenza A virus (A/Puerto Rico/8/1934(H1N1)) More |
| Total number of polymer chains | 2 |
| Total formula weight | 63113.82 |
| Authors | Lin, T.H.,Zhu, Y.,Wilson, I.A. (deposition date: 2024-01-18, release date: 2024-06-05, Last modification date: 2024-10-30) |
| Primary citation | Kitamura, S.,Lin, T.H.,Lee, C.D.,Takamura, A.,Kadam, R.U.,Zhang, D.,Zhu, X.,Dada, L.,Nagai, E.,Yu, W.,Yao, Y.,Sharpless, K.B.,Wilson, I.A.,Wolan, D.W. Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry. Proc.Natl.Acad.Sci.USA, 121:e2310677121-e2310677121, 2024 Cited by PubMed Abstract: Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry-based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets. PubMed: 38753503DOI: 10.1073/pnas.2310677121 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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