8wsp

Crystal structure of SFTSV Gn and antibody SF5

spinqualitylabelsall models 8wsp, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8wsp is a 6 chain structure with sequence from Homo sapiens and SFTS virus SD4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.51Å Ligands: MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection. Bispecific antibodies targeting two glycoproteins on SFTSV exhibit synergistic neutralization and protection in a mouse model.,Chang Z, Gao D, Liao L, Sun J, Zhang G, Zhang X, Wang F, Li C, Oladejo BO, Li S, Chai Y, Hu Y, Lu X, Xiao H, Qi J, Chen Z, Gao F, Wu Y Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2400163121. doi: , 10.1073/pnas.2400163121. Epub 2024 Jun 3. PMID:38830098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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