{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:29:13Z","timestamp":1790947753530,"version":"4.1.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1K99GM135529"],"award-info":[{"award-number":["1K99GM135529"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRG-2297-17"],"award-info":[{"award-number":["DRG-2297-17"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI111825"],"award-info":[{"award-number":["U19AI111825"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["OD022552"],"award-info":[{"award-number":["OD022552"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,11,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>During the ongoing COVID-19 pandemic, protein engineering offers a rapid and powerful approach for building therapeutics to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We use computational design, affinity maturation, and fusion to dimerization domains to engineer \u201creceptor traps\u201d based on wild-type angiotensin-converting enzyme II (ACE2), the target for viral spike-mediated SARS-CoV-2 entry into cells. The optimized ACE2 receptor traps neutralize authentic SARS-CoV-2 infections as effectively as high-affinity antibodies isolated from convalescent patients and also bind viral spike proteins from other coronaviruses known to cause respiratory diseases. ACE2 receptor traps have large binding interfaces and block the entire receptor binding interface, limiting the potential impact of viral escape mutations.<\/jats:p>","DOI":"10.1073\/pnas.2016093117","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T20:01:02Z","timestamp":1603396862000},"page":"28046-28055","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":255,"title":["Engineered ACE2 receptor traps potently neutralize SARS-CoV-2"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-881X","authenticated-orcid":false,"given":"Anum","family":"Glasgow","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6699-8983","authenticated-orcid":false,"given":"Jeff","family":"Glasgow","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5128-6542","authenticated-orcid":false,"given":"Daniel","family":"Limonta","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada;"},{"name":"Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6171-5443","authenticated-orcid":false,"given":"Irene","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-3206","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-5368","authenticated-orcid":false,"given":"Matthew A.","family":"Nix","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4332-2697","authenticated-orcid":false,"given":"Nicholas J.","family":"Rettko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4190-2823","authenticated-orcid":false,"given":"Shoshana","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Yamin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Kao","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-4388","authenticated-orcid":false,"given":"Oren S.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-9041","authenticated-orcid":false,"given":"Jeffrey V.","family":"Ravetch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-6964","authenticated-orcid":false,"given":"Arun P.","family":"Wiita","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-4974","authenticated-orcid":false,"given":"Kevin K.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-2732","authenticated-orcid":false,"given":"Shion A.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-2856","authenticated-orcid":false,"given":"Xin X.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-3545","authenticated-orcid":false,"given":"Tom C.","family":"Hobman","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada;"},{"name":"Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada;"},{"name":"Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Kortemme","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-5519","authenticated-orcid":false,"given":"James A.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;"},{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2381-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2241"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0831"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2456-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.025"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","unstructured":"W. Li Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models. https:\/\/www.biorxiv.org\/content\/10.1101\/2020.05.13.093088v2 (2 June 2020).","DOI":"10.1101\/2020.05.13.093088"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-0469-6"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","unstructured":"S. Miersch . Synthetic antibodies neutralize SARS-CoV-2 infection of mammalian cells. https:\/\/doi.org\/10.1101\/2020.06.05.137349 (10 June 2020).","DOI":"10.1101\/2020.06.05.137349"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16048-4"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0072-7"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1823-x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","unstructured":"I. Lui Trimeric SARS-CoV-2 spike interacts with dimeric ACE2 with limited intra-spike avidity. https:\/\/doi.org\/10.1101\/2020.05.21.109157 (21 May 2020).","DOI":"10.1101\/2020.05.21.109157"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2180-5"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2349-y"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb7269"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6952"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02232-14"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2179-y"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.045"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"E. Procko The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2. http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.03.16.994236 (11 May 2020).","DOI":"10.1101\/2020.03.16.994236"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116480"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202485799"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2192004pl2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004335"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","unstructured":"Y. Li Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1. http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.04.10.032342 (11 April 2020).","DOI":"10.1101\/2020.04.10.032342"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201600696"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1636"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25726"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"H. Mou Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7337384\/ (30 June 2020).","DOI":"10.1101\/2020.06.29.178459"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2762"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2507"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","unstructured":"T. Zhou Cryo-EM structures delineate a pH-dependent switch that mediates endosomal positioning of SARS-CoV-2 spike receptor-binding domains. http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.07.04.187989 (31 July 2020).","DOI":"10.1101\/2020.07.04.187989"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzl003"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzv050"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.04756.x"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc5902"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908837106"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.92"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2009.10.010"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-019-0224-z"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217996110"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/9.7.617"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3907"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1086\/317622"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.06.021"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","unstructured":"X. Miao A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: Implications for therapy. https:\/\/doi.org\/10.1101\/2020.06.14.147868 (15 June 2020).","DOI":"10.1101\/2020.06.14.147868"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/357420a0"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzq002"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(02)00018-0"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12050513"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2016093117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2016093117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:21:27Z","timestamp":1649834487000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2016093117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":54,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2020,11,10]]}},"alternative-id":["10.1073\/pnas.2016093117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2016093117","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.738888191.793584247","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.31.231746","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]},"assertion":[{"value":"2020-10-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}