35WK
Crystal structure of the core catalytic domain of human inositol phosphate multikinase in complex with an inhibitor UNC7844
This is a non-PDB format compatible entry.
Summary for 35WK
| Entry DOI | 10.2210/pdb35wk/pdb |
| Descriptor | Inositol polyphosphate multikinase, (5P)-3-([1,1'-biphenyl]-4-yl)-5-(1H-tetrazol-5-yl)-2,1-benzoxazole (3 entities in total) |
| Functional Keywords | structure-based inhibitor development, kinase, inhibitor, inositol polyphosphate, transferase, transferase-transferase inhibitor complex |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30167.26 |
| Authors | Wang, H. (deposition date: 2026-05-20, release date: 2026-09-23, Last modification date: 2026-10-07) |
| Primary citation | Shats, I.,Wang, H.,Zhou, Y.,Gu, C.,Carr, A.,Guardia, C.M.,Shears, S.,Stanley, R.,Zhang, Q.,Blind, R.D.,Wang, X.,Li, X. Host soluble inositol phosphate signaling promotes coronavirus replication. Biorxiv, 2026 Cited by PubMed Abstract: Coronaviruses rely extensively on host pathways for replication, making host-directed therapies an attractive strategy for broad-spectrum antivirals with reduced risk of viral resistance. Here we identify the host soluble inositol phosphate pathway as a previously unrecognized dependency for coronavirus infection. Genetic or pharmacologic inhibition of several kinases in this pathway markedly suppresses replication of both alpha- and betacoronaviruses, while increasing pathway activity promotes viral replication. We developed UNC7844, a potent multi-target inhibitor of these kinases, which reduces coronavirus replication by more than four orders of magnitude in cultured cells and suppresses coronavirus infection in mice. Mechanistically, UNC7844 suppresses inositol (pyro)phosphates production, disrupts phosphoinositide homeostasis, and impairs late endosomal dynamics, blocking early post-entry steps required for viral genome release and replication. Together, our findings establish the soluble inositol (pyro)phosphate pathway as an important regulator of coronavirus infection and highlight its inhibition as a promising host-directed antiviral strategy. PubMed: 42779723DOI: 10.64898/2026.09.12.751050 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.646 Å) |
Structure validation
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