9lf8
Structure of MPXV M1R and mMM1-16 Fab complex
Structural highlights
FunctionPG095_MONPV Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consisting of lipid mixing of the viral and cellular membranes and subsequent pore formation.[UniProtKB:P07612] Publication Abstract from PubMedThe global outbreak of the mpox in humans, caused by the mpox virus (MPXV), underscores the urgent need for safe and effective therapeutics. In this study, we characterized the dominant MPXV immunogens, M1R and B6R, by sequencing monoclonal antibodies (MAbs) from the immunized mice and analyzing their epitopes and functions through in vitro and in vivo assessments of binding and antiviral activities. Several broadly effective anti-M1R and anti-B6R neutralizing MAbs were identified and they exhibited enhanced antiviral effects against MPXV or vaccinia virus (VACV) when used in antibody cocktail and bispecific antibody designs. Notably, the VH-CH1 switch region-inserting format of bispecific antibodies exhibited robust protective efficacy against VACV in a mouse model. Collectively, our study characterized the epitope and functional maps of anti-M1R and anti-B6R MAbs and developed promising broad-spectrum antibody candidates for the treatment of MPXV and other orthopoxvirus infections. Anti-M1R/B6R antibody characterization and bispecific design for enhanced orthopoxvirus protection.,Zhao R, Wu L, Zhang Y, Ma J, Liu D, Zheng Y, Kong T, Ma R, Gao Z, Chai Y, Liu Y, Tian Y, Xia Y, Hou Y, Lu J, Cong Z, Huang B, Tan W, Xue J, Gao GF, Wang Q EMBO Mol Med. 2025 Sep 8. doi: 10.1038/s44321-025-00299-z. PMID:40921877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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