8u5l

MAU868, a novel human-derived monoclonal neutralizing antibody targeting BK virus VP1

spinqualitylabelsall models 8u5l, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8u5l is a 10 chain structure with sequence from Homo sapiens and Human polyomavirus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7VLA4_POVBK Forms an icosahedral capsid with a T=7 symmetry.[PIRNR:PIRNR003376] Publication Abstract from PubMed Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human immunoglobulin (Ig) G1 monoclonal antibody that binds the major capsid protein, VP1, of BKPyV with picomolar affinity, neutralizes infection by the 4 major BKPyV genotypes (EC(50) ranging from 0.009-0.093 mug/mL; EC(90) ranging from 0.102-4.160 mug/mL), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified 3 key contact residues in VP1 (Y169, R170, and K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease. Nonclinical and clinical characterization of MAU868, a novel human-derived monoclonal neutralizing antibody targeting BK polyomavirus VP1.,Abend JR, Sathe A, Wrobel MB, Knapp M, Xu L, Zhao L, Kim P, Desai S, Nguyen A, Leber XC, Hein A, Scharenberg M, Shaul J, Ornelas E, Wong K, Pietzonka T, Sterling LM, Hodges MR, Pertel P, Traggiai E, Patick AK, Kovacs SJ Am J Transplant. 2024 Jul 10:S1600-6135(24)00424-6. doi: , 10.1016/j.ajt.2024.07.002. PMID:38996969 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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