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Crystal structure of the envelope glycoprotein complex of Puumala virus in complex with the scFv fragment of the broadly neutralizing human antibody ADI-42898Crystal structure of the envelope glycoprotein complex of Puumala virus in complex with the scFv fragment of the broadly neutralizing human antibody ADI-42898
Structural highlights
FunctionA0A0B4U5I0_9VIRU A0A6M3W7M6_9VIRU Publication Abstract from PubMedEmerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic. Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody.,Mittler E, Serris A, Esterman ES, Florez C, Polanco LC, O'Brien CM, Slough MM, Tynell J, Groning R, Sun Y, Abelson DM, Wec AZ, Haslwanter D, Keller M, Ye C, Bakken RR, Jangra RK, Dye JM, Ahlm C, Rappazzo CG, Ulrich RG, Zeitlin L, Geoghegan JC, Bradfute SB, Sidoli S, Forsell MNE, Strandin T, Rey FA, Herbert AS, Walker LM, Chandran K, Guardado-Calvo P Sci Transl Med. 2023 Jun 14;15(700):eadg1855. doi: 10.1126/scitranslmed.adg1855. , Epub 2023 Jun 14. PMID:37315110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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