9isf

Crystal structure of nanobody 14 in complex with HSV-2 gD

spinqualitylabelsall models 9isf, resolution 3.72Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9isf is a 2 chain structure with sequence from Human alphaherpesvirus 2 and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.72Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1W6QD44_HHV2 Publication Abstract from PubMed Herpes simplex virus (HSV) causes significant health burden worldwide. Currently used antiviral drugs are effective but resistance can occur. Here, we report two high-affinity neutralizing nanobodies, namely Nb14 and Nb32, that target non-overlapping epitopes in HSV gD. Nb14 binds a neutralization epitope located in the N-A' interloop, which prevents the interaction between gD and gH/gL during the second step of conformational changes during membrane fusion after virus attachment. The bispecific nanobody dimer (Nb14-32-Fc) exhibits high potency in vitro and in vivo. Mechanistically, Nb14-32-Fc neutralizes HSVs at both the pre-and post-attachment stages and prevents cell-to-cell spread in vitro. Administration of Nb14-32-Fc at low dosage of 1 mg/kg provides 100% protection in an HSV-1 infection male mouse model and an HSV-2 infection female mouse model. Our results demonstrate that Nb14-32-Fc could serve as a promising drug candidate for treatment of HSV infection, especially in the cases of antiviral drug resistance and severe herpes encephalitis. A potent protective bispecific nanobody targeting Herpes simplex virus gD reveals vulnerable epitope for neutralizing.,Hu J, Tan H, Wang M, Deng S, Liu M, Zheng P, Wang A, Guo M, Wang J, Li J, Qiu H, Yao C, Zhu Z, Hasi C, Pan D, He H, Huang C, Shang Y, Zhu S, Jin T Nat Commun. 2025 May 6;16(1):4196. doi: 10.1038/s41467-025-58669-7. PMID:40328740 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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