{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:29:09Z","timestamp":1788276549064,"version":"build-2803163510"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Discov"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mpox virus (MPXV) poses an increasing global health threat, as underscored by two World Health Organization declarations of Public Health Emergencies of International Concern, particularly after the emergence of a novel Clade Ib strain that exhibited high human-to-human transmissibility in the Democratic Republic of the Congo. However, the treatment options for MPXV infection remain extremely limited. To address this unmet need, we established an integrated platform combining single-cell transcriptomics and deep learning-based structural prediction to discover effective human monoclonal antibodies against MPXV. By integrating computational prediction with experimental validation, we identified five neutralizing antibodies targeting the following distinct viral forms: BA345, MA42, and MA49, which engage the extracellular enveloped virus-associated A35R glycoprotein; BAL31, which binds intracellular mature virus (IMV) protein A29L; and HB05, which targets IMV antigen H3L. Importantly, the elite monoclonal antibody BA345 conferred effective protection against MPXV and vaccinia virus both in vitro and in vivo. Combined in silico structure prediction and X-ray crystallography revealed a highly conserved epitope shared across orthopoxviruses. Surface plasmon resonance measurements revealed nanomolar equilibrium dissociation constants of BA345 for A35R homologs, corroborating its cross-reactive, broad-spectrum neutralizing activity against orthopoxviruses. Moreover, the BA345\/BAL31 and MA49\/BAL31 antibody cocktails developed in this study conferred robust therapeutic protection in MPXV-infected animals, substantially reducing disease severity and viral load. Our findings not only establish a practical paradigm for antibody discovery through the integration of deep learning-driven structure prediction with single-cell multiomics but also inform next-generation biodefense countermeasures against MPXV and related orthopoxviruses.<\/jats:p>","DOI":"10.1038\/s41421-026-00916-2","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:59:36Z","timestamp":1788271176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-protective human antibodies against the Mpox virus discovered through structure-guided screening"],"prefix":"10.1038","volume":"12","author":[{"given":"Dongdong","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5796-8851","authenticated-orcid":false,"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitian","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-6185","authenticated-orcid":false,"given":"Zixian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-1411","authenticated-orcid":false,"given":"Haisheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8109-7515","authenticated-orcid":false,"given":"Yu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"916_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28206","volume":"95","author":"AG Mukherjee","year":"2023","unstructured":"Mukherjee, A. G. et al. The pathophysiological and immunological background of the monkeypox virus infection: An update. J. Med. Virol. 95, e28206 (2023).","journal-title":"J. Med. Virol."},{"key":"916_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2023.106960","volume":"245","author":"J Nyame","year":"2023","unstructured":"Nyame, J. et al. Challenges in the treatment and prevention of monkeypox infection; a comprehensive review. Acta Trop. 245, 106960 (2023).","journal-title":"Acta Trop."},{"key":"916_CR3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.virs.2022.07.006","volume":"37","author":"Q Gong","year":"2022","unstructured":"Gong, Q., Wang, C., Chuai, X. & Chiu, S. Monkeypox virus: a re-emergent threat to humans. Virol. Sin. 37, 477\u2013482 (2022).","journal-title":"Virol. Sin."},{"key":"916_CR4","doi-asserted-by":"crossref","unstructured":"Shchelkunova, G. A. & Shchelkunov, S. N. Smallpox, monkeypox and other human orthopoxvirus infections. Viruses 15, 103 (2022).","DOI":"10.3390\/v15010103"},{"key":"916_CR5","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1080\/22221751.2022.2095309","volume":"11","author":"Y Xiang","year":"2022","unstructured":"Xiang, Y. & White, A. Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters. Emerg. Microbes Infect. 11, 1768\u20131777 (2022).","journal-title":"Emerg. Microbes Infect."},{"key":"916_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1360586","volume":"14","author":"E Alakunle","year":"2024","unstructured":"Alakunle, E. et al. A comprehensive review of monkeypox virus and mpox characteristics. Front. Cell. Infect. Microbiol. 14, 1360586 (2024).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"916_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27931","volume":"95","author":"NL Bragazzi","year":"2023","unstructured":"Bragazzi, N. L. et al. Epidemiological trends and clinical features of the ongoing monkeypox epidemic: a preliminary pooled data analysis and literature review. J. Med. Virol. 95, e27931 (2023).","journal-title":"J. Med. Virol."},{"key":"916_CR8","unstructured":"WHO. Mpox (Monkeypox) Outbreak: Global Trends, https:\/\/worldhealthorg.shinyapps.io\/mpx_global\/ (2025)."},{"key":"916_CR9","unstructured":"Africa Centres for Disease Control and Prevention. Africa CDC Epidemic Intelligence Weekly Report, https:\/\/africacdc.org\/download\/africa-cdc-weekly-event-based-surveillance-report-august-2024\/ (2024)."},{"key":"916_CR10","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.3390\/v16101620","volume":"16","author":"K Protopapas","year":"2024","unstructured":"Protopapas, K., Dimopoulou, D., Kalesis, N., Akinosoglou, K. & Moschopoulos, C. D. Mpox and Lessons Learned in the Light of the Recent Outbreak: A Narrative Review. Viruses 16, 1620 (2024).","journal-title":"Viruses"},{"key":"916_CR11","doi-asserted-by":"crossref","unstructured":"Zheng, W. et al. Improving deep learning protein monomer and complex structure prediction using DeepMSA2 with huge metagenomics data. Nat. Methods 21, 279\u2013289 (2024).","DOI":"10.1038\/s41592-023-02130-4"},{"key":"916_CR12","doi-asserted-by":"publisher","first-page":"5540","DOI":"10.1016\/j.cell.2024.08.043","volume":"187","author":"EM Mucker","year":"2024","unstructured":"Mucker, E. M. et al. Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates. Cell 187, 5540\u20135553.e10 (2024).","journal-title":"Cell"},{"key":"916_CR13","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41577-022-00775-4","volume":"22","author":"FM Lum","year":"2022","unstructured":"Lum, F. M. et al. Monkeypox: disease epidemiology, host immunity and clinical interventions. Nat. Rev. Immunol. 22, 597\u2013613 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"916_CR14","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-022-02090-w","volume":"29","author":"LM Zaeck","year":"2023","unstructured":"Zaeck, L. M. et al. Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals. Nat. Med. 29, 270\u2013278 (2023).","journal-title":"Nat. Med."},{"key":"916_CR15","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/tropicalmed1010008","volume":"1","author":"K Brown","year":"2016","unstructured":"Brown, K. & Leggat, P. A. Human monkeypox: current state of knowledge and implications for the future. Trop. Med. Infect. Dis. 1, 8 (2016).","journal-title":"Trop. Med. Infect. Dis."},{"key":"916_CR16","doi-asserted-by":"crossref","unstructured":"Neff, J. et al. Monitoring the safety of a smallpox vaccination program in the United States: report of the joint Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices and the Armed Forces Epidemiological Board. Clin. Infect. Dis. 46, S258\u2013S270 (2008).","DOI":"10.1086\/524749"},{"key":"916_CR17","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/j.cell.2024.02.011","volume":"187","author":"AN Nitido","year":"2024","unstructured":"Nitido, A. N. & Balazs, A. B. mRNA-based monkeypox virus vaccine prevents disease in non-human primates. Cell 187, 1360\u20131362 (2024).","journal-title":"Cell"},{"key":"916_CR18","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.cell.2024.01.017","volume":"187","author":"A Zuiani","year":"2024","unstructured":"Zuiani, A. et al. A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease. Cell 187, 1363\u20131373.e12 (2024).","journal-title":"Cell"},{"key":"916_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39267-x","volume":"14","author":"Y Guo","year":"2023","unstructured":"Guo, Y. et al. Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection. Nat. Commun. 14, 3537 (2023).","journal-title":"Nat. Commun."},{"key":"916_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36761-0","volume":"14","author":"H Yu","year":"2023","unstructured":"Yu, H. et al. Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants. Nat. Commun. 14, 1058 (2023).","journal-title":"Nat. Commun."},{"key":"916_CR21","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1208\/s12248-020-00532-2","volume":"23","author":"J Majumder","year":"2021","unstructured":"Majumder, J. & Minko, T. Recent developments on therapeutic and diagnostic approaches for COVID-19. AAPS J. 23, 14 (2021).","journal-title":"AAPS J."},{"key":"916_CR22","doi-asserted-by":"publisher","first-page":"6266","DOI":"10.1016\/j.cell.2025.07.040","volume":"188","author":"A Meola","year":"2025","unstructured":"Meola, A. et al. Structural basis of poxvirus fusion regulation and anti-A16\/G9 antibody-mediated neutralization and protection. Cell 188, 6266\u20136282.e18 (2025).","journal-title":"Cell"},{"key":"916_CR23","doi-asserted-by":"publisher","first-page":"100185","DOI":"10.1016\/j.cellin.2024.100185","volume":"3","author":"XM Yi","year":"2024","unstructured":"Yi, X. M., Lei, Y. L., Li, M., Zhong, L. & Li, S. The monkeypox virus-host interplays. Cell Insight 3, 100185 (2024).","journal-title":"Cell Insight"},{"key":"916_CR24","volume":"16","author":"S Mani","year":"2024","unstructured":"Mani, S. et al. Epidemiology, virology, and mutation landscape of monkeypox virus from past to present. Cureus 16, e67872 (2024).","journal-title":"Cureus"},{"key":"916_CR25","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1007\/s11427-023-2378-x","volume":"66","author":"N Zhang","year":"2023","unstructured":"Zhang, N. et al. Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity. Sci. China Life Sci. 66, 2329\u20132341 (2023).","journal-title":"Sci. China Life Sci."},{"key":"916_CR26","doi-asserted-by":"publisher","first-page":"5020","DOI":"10.1128\/JVI.02933-15","volume":"90","author":"K Singh","year":"2016","unstructured":"Singh, K. et al. The vaccinia virus H3 envelope protein, a major target of neutralizing antibodies, exhibits a glycosyltransferase fold and binds UDP-glucose. J. Virol. 90, 5020\u20135030 (2016).","journal-title":"J. Virol."},{"key":"916_CR27","doi-asserted-by":"publisher","first-page":"2401931","DOI":"10.1080\/22221751.2024.2401931","volume":"13","author":"Z Ren","year":"2024","unstructured":"Ren, Z. et al. Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus. Emerg. Microbes Infect. 13, 2401931 (2024).","journal-title":"Emerg. Microbes Infect."},{"key":"916_CR28","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.antiviral.2017.05.002","volume":"144","author":"M Zaitseva","year":"2017","unstructured":"Zaitseva, M. et al. Development of an animal model of progressive vaccinia in nu\/nu mice and the use of bioluminescence imaging for assessment of the efficacy of monoclonal antibodies against vaccinial B5 and L1 proteins. Antivir. Res. 144, 8\u201320 (2017).","journal-title":"Antivir. Res."},{"key":"916_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.126384","volume":"42","author":"M Tan","year":"2024","unstructured":"Tan, M. et al. Systematic evaluation of the induction of efficient neutralizing antibodies by recombinant multicomponent subunit vaccines against monkeypox virus. Vaccine 42, 126384 (2024).","journal-title":"Vaccine"},{"key":"916_CR30","doi-asserted-by":"publisher","first-page":"1112816","DOI":"10.3389\/fimmu.2023.1112816","volume":"14","author":"C Tan","year":"2023","unstructured":"Tan, C., Zhu, F., Pan, P., Wu, A. & Li, C. Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches. Front. Immunol. 14, 1112816 (2023).","journal-title":"Front. Immunol."},{"key":"916_CR31","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1074\/jbc.M117.814541","volume":"293","author":"MH Matho","year":"2018","unstructured":"Matho, M. H. et al. Structure-function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8. J. Biol. Chem. 293, 390\u2013401 (2018).","journal-title":"J. Biol. Chem."},{"key":"916_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105392","volume":"109","author":"T Kong","year":"2024","unstructured":"Kong, T. et al. Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus. EBioMedicine 109, 105392 (2024).","journal-title":"EBioMedicine"},{"key":"916_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48312-2","volume":"15","author":"R Zhao","year":"2024","unstructured":"Zhao, R. et al. Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections. Nat. Commun. 15, 4660 (2024).","journal-title":"Nat. Commun."},{"key":"916_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58180-z","volume":"16","author":"Y Qu","year":"2025","unstructured":"Qu, Y. et al. Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus. Nat. Commun. 16, 3100 (2025).","journal-title":"Nat. Commun."},{"key":"916_CR35","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev.micro.57.030502.091037","volume":"57","author":"GL Smith","year":"2003","unstructured":"Smith, G. L., Murphy, B. J. & Law, M. Vaccinia virus motility. Annu. Rev. Microbiol. 57, 323\u2013342 (2003).","journal-title":"Annu. Rev. Microbiol."},{"key":"916_CR36","doi-asserted-by":"publisher","first-page":"688","DOI":"10.3390\/v4050688","volume":"4","author":"B Moss","year":"2012","unstructured":"Moss, B. Poxvirus cell entry: how many proteins does it take? Viruses 4, 688\u2013707 (2012).","journal-title":"Viruses"},{"key":"916_CR37","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41590-023-01715-7","volume":"25","author":"H Wang","year":"2024","unstructured":"Wang, H. et al. Rational design of a \u2018two-in-one\u2019 immunogen DAM drives potent immune response against mpox virus. Nat. Immunol. 25, 307\u2013315 (2024).","journal-title":"Nat. Immunol."},{"key":"916_CR38","doi-asserted-by":"publisher","first-page":"4113","DOI":"10.1128\/JVI.77.7.4113-4126.2003","volume":"77","author":"BM Ward","year":"2003","unstructured":"Ward, B. M., Weisberg, A. S. & Moss, B. Mapping and functional analysis of interaction sites within the cytoplasmic domains of the vaccinia virus A33R and A36R envelope proteins. J. Virol. 77, 4113\u20134126 (2003).","journal-title":"J. Virol."},{"key":"916_CR39","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1099\/0022-1317-83-1-209","volume":"83","author":"M Law","year":"2002","unstructured":"Law, M., Hollinshead, R. & Smith, G. L. Antibody-sensitive and antibody-resistant cell-to-cell spread by vaccinia virus: role of the A33R protein in antibody-resistant spread. J. Gen. Virol. 83, 209\u2013222 (2002).","journal-title":"J. Gen. Virol."},{"key":"916_CR40","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1128\/JVI.75.1.303-310.2001","volume":"75","author":"EJ Wolffe","year":"2001","unstructured":"Wolffe, E. J., Weisberg, A. S. & Moss, B. The vaccinia virus A33R protein provides a chaperone function for viral membrane localization and tyrosine phosphorylation of the A36R protein. J. Virol. 75, 303\u2013310 (2001).","journal-title":"J. Virol."},{"key":"916_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41628-5","volume":"14","author":"F Hou","year":"2023","unstructured":"Hou, F. et al. mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge. Nat. Commun. 14, 5925 (2023).","journal-title":"Nat. Commun."},{"key":"916_CR42","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.1016\/j.cell.2025.08.004","volume":"188","author":"RF Fantin","year":"2025","unstructured":"Fantin, R. F. et al. Human monoclonal antibodies targeting A35 protect from death caused by mpox. Cell 188, 6236\u20136252.e18 (2025).","journal-title":"Cell"},{"key":"916_CR43","doi-asserted-by":"publisher","first-page":"6253","DOI":"10.1016\/j.cell.2025.08.005","volume":"188","author":"B Ju","year":"2025","unstructured":"Ju, B. et al. Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection. Cell 188, 6253\u20136265.e14 (2025).","journal-title":"Cell"},{"key":"916_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22926-2","volume":"12","author":"Y Guo","year":"2021","unstructured":"Guo, Y. et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes. Nat. Commun. 12, 2623 (2021).","journal-title":"Nat. Commun."},{"key":"916_CR45","doi-asserted-by":"publisher","first-page":"e3001209","DOI":"10.1371\/journal.pbio.3001209","volume":"19","author":"D Fu","year":"2021","unstructured":"Fu, D. et al. Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes. PLoS Biol. 19, e3001209 (2021).","journal-title":"PLoS Biol."},{"key":"916_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111845","volume":"41","author":"Y Cao","year":"2022","unstructured":"Cao, Y. et al. Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents. Cell Rep. 41, 111845 (2022).","journal-title":"Cell Rep."},{"key":"916_CR47","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41422-020-00444-y","volume":"31","author":"H Yao","year":"2021","unstructured":"Yao, H. et al. Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection. Cell Res. 31, 25\u201336 (2021).","journal-title":"Cell Res."},{"key":"916_CR48","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8336","volume":"8","author":"Q Wang","year":"2016","unstructured":"Wang, Q. et al. Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus. Sci. Transl. Med. 8, 369ra179 (2016).","journal-title":"Sci. Transl. Med."},{"key":"916_CR49","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1016\/j.cell.2019.11.003","volume":"179","author":"I Setliff","year":"2019","unstructured":"Setliff, I. et al. High-throughput mapping of b cell receptor sequences to antigen specificity. Cell 179, 1636\u20131646.e15 (2019).","journal-title":"Cell"},{"key":"916_CR50","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1002\/prot.70059","volume":"94","author":"Q Wuyun","year":"2025","unstructured":"Wuyun, Q. et al. Alternative conformation prediction using deep learning with multi-MSA strategy and structural clustering in CASP16. Proteins 94, 348\u2013361 (2025).","journal-title":"Proteins"},{"key":"916_CR51","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41587-025-02654-4","volume":"44","author":"W Zheng","year":"2025","unstructured":"Zheng, W. et al. Deep-learning-based single-domain and multidomain protein structure prediction with D-I-TASSER. Nat. Biotechnol. 44, 641\u2013653 (2025).","journal-title":"Nat. Biotechnol."},{"key":"916_CR52","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1002\/prot.26585","volume":"91","author":"W Zheng","year":"2023","unstructured":"Zheng, W., Wuyun, Q., Freddolino, L. & Zhang, Y. Integrating deep learning, threading alignments, and a multi-MSA strategy for high-quality protein monomer and complex structure prediction in CASP15. Proteins 91, 1684\u20131703 (2023).","journal-title":"Proteins"},{"key":"916_CR53","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cell.2020.05.025","volume":"182","author":"Y Cao","year":"2020","unstructured":"Cao, Y. et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients\u2019 B cells. Cell 182, 73\u201384.e16 (2020).","journal-title":"Cell"},{"key":"916_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1203410","volume":"14","author":"D Tang","year":"2023","unstructured":"Tang, D. et al. Recombinant proteins A29L, M1R, A35R, and B6R vaccination protects mice from mpox virus challenge. Front. Immunol. 14, 1203410 (2023).","journal-title":"Front. Immunol."},{"key":"916_CR55","doi-asserted-by":"publisher","first-page":"e1003563","DOI":"10.1371\/journal.ppat.1003563","volume":"9","author":"TH Chang","year":"2013","unstructured":"Chang, T. H. et al. Crystal structure of vaccinia viral A27 protein reveals a novel structure critical for its function and complex formation with A26 protein. PLoS Pathog. 9, e1003563 (2013).","journal-title":"PLoS Pathog."},{"key":"916_CR56","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1099\/vir.0.80831-0","volume":"86","author":"GC Carter","year":"2005","unstructured":"Carter, G. C., Law, M., Hollinshead, M. & Smith, G. L. Entry of the vaccinia virus intracellular mature virion and its interactions with glycosaminoglycans. J. Gen. Virol. 86, 1279\u20131290 (2005).","journal-title":"J. Gen. Virol."},{"key":"916_CR57","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.semcdb.2016.07.015","volume":"60","author":"B Moss","year":"2016","unstructured":"Moss, B. Membrane fusion during poxvirus entry. Semin. Cell Dev. Biol. 60, 89\u201396 (2016).","journal-title":"Semin. Cell Dev. Biol."},{"key":"916_CR58","doi-asserted-by":"publisher","first-page":"21896","DOI":"10.1021\/jacs.5c05014","volume":"147","author":"J Wang","year":"2025","unstructured":"Wang, J. et al. Structural basis and rational design of nucleotide analogue inhibitor evading the SARS-CoV-2 proofreading enzyme. J. Am. Chem. Soc. 147, 21896\u201321906 (2025).","journal-title":"J. Am. Chem. Soc."},{"key":"916_CR59","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1093\/procel\/pwaf051","volume":"16","author":"L Wang","year":"2025","unstructured":"Wang, L. et al. Discovery and structural investigation of Varicella-Zoster virus gE-neutralizing antibodies isolated from a convalescent patient. Protein Cell 16, 1054\u20131059 (2025).","journal-title":"Protein Cell"},{"key":"916_CR60","doi-asserted-by":"publisher","first-page":"W34","DOI":"10.1093\/nar\/gkt382","volume":"41","author":"J Ye","year":"2013","unstructured":"Ye, J., Ma, N., Madden, T. L. & Ostell, J. M. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 41, W34\u2013W40 (2013).","journal-title":"Nucleic Acids Res."},{"key":"916_CR61","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1093\/bioinformatics\/btz863","volume":"36","author":"C Zhang","year":"2020","unstructured":"Zhang, C., Zheng, W., Mortuza, S. M., Li, Y. & Zhang, Y. DeepMSA: constructing deep multiple sequence alignment to improve contact prediction and fold-recognition for distant-homology proteins. Bioinformatics 36, 2105\u20132112 (2020).","journal-title":"Bioinformatics"},{"key":"916_CR62","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"J Abramson","year":"2024","unstructured":"Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493\u2013500 (2024).","journal-title":"Nature"},{"key":"916_CR63","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nmeth.1818","volume":"9","author":"M Remmert","year":"2011","unstructured":"Remmert, M., Biegert, A., Hauser, A. & S\u00f6ding, J. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9, 173\u2013175 (2011).","journal-title":"Nat. Methods"},{"key":"916_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-431","volume":"11","author":"LS Johnson","year":"2010","unstructured":"Johnson, L. S., Eddy, S. R. & Portugaly, E. Hidden Markov model speed heuristic and iterative HMM search procedure. BMC Bioinform. 11, 431 (2010).","journal-title":"BMC Bioinform."},{"key":"916_CR65","doi-asserted-by":"publisher","first-page":"11339","DOI":"10.1128\/JVI.01491-14","volume":"88","author":"T Kaever","year":"2014","unstructured":"Kaever, T. et al. Potent neutralization of vaccinia virus by divergent murine antibodies targeting a common site of vulnerability in L1 protein. J. Virol. 88, 11339\u201311355 (2014).","journal-title":"J. Virol."},{"key":"916_CR66","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"916_CR67","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"916_CR68","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/prot.20264","volume":"57","author":"Y Zhang","year":"2004","unstructured":"Zhang, Y. & Skolnick, J. Scoring function for automated assessment of protein structure template quality. Proteins 57, 702\u2013710 (2004).","journal-title":"Proteins"},{"key":"916_CR69","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/s41592-022-01585-1","volume":"19","author":"C Zhang","year":"2022","unstructured":"Zhang, C., Shine, M., Pyle, A. M. & Zhang, Y. US-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes. Nat. Methods 19, 1109\u20131115 (2022).","journal-title":"Nat. Methods"}],"container-title":["Cell Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41421-026-00916-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41421-026-00916-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41421-026-00916-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:12:24Z","timestamp":1788275544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41421-026-00916-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["916"],"URL":"https:\/\/doi.org\/10.1038\/s41421-026-00916-2","relation":{},"ISSN":["2056-5968"],"issn-type":[{"value":"2056-5968","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"6 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Y.G., D.S., and Z.J. declare the following competing interests: patent applications have been filed for the sequences of the monkeypox virus-neutralizing antibodies MA42, MA49, BA345, BAL31, and HB05 described in this work. All other authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"64"}}