{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:03Z","timestamp":1785435723993,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,5]]},"group-title":"Microbiology","reference-count":97,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Pendleton Laboratory Fund for Pediatric Infectious Diseases, University of Virginia"},{"name":"Manning Fund for COVID-19 Research, University of Virginia"},{"DOI":"10.13039\/100008222","name":"Ivy Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008222","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Virginia Summer Research Internship Program"},{"award":["AI176515"],"award-info":[{"award-number":["AI176515"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute, National Institutes of Health","award":["P30-CA044579"],"award-info":[{"award-number":["P30-CA044579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Many people with acute COVID-19 have clinical disease not clearly attributable to viral replication and many COVID-19 convalescents are affected by post-acute sequelae of COVID-19 (PASC, or long COVID, LC). LC has severely affected public health and economies worldwide. Features of LC including blood pressure dysregulation, coagulopathies, high levels of inflammation, and neuropsychiatric complaints. The mechanisms responsible for the pathogenesis of some of COVID-19\u2019s clinical features and LC have not been well established. The host cell receptor for SARS-CoV-2 is human angiotensin converting enzyme 2 (ACE2), which binds the SARS-CoV-2 spike protein receptor-binding domain (RBD) to initiate infection. We hypothesized that some people may produce anti-RBD antibodies that sufficiently resemble ACE2 structure to have ACE2-like catalytic activity after infection. Those antibodies, ACE2-like abzymes, may contribute to the pathogenesis of LC. Our previous studies showed that ACE2-like activity was associated with immunoglobulin in some acute and convalescent COVID-19 patients. ACE2-like catalytic activity correlated with blood pressure changes following a moderate exercise challenge in people convalescing from COVID-19. To further establish that ACE2-like activity could be attributed to antibodies, we screened human monoclonal antibodies (mAbs) against SARS-CoV-2 spike protein from 3 different research centers and others purchased from a commercial source for ACE2-like catalytic activity. We identified 4 human monoclonal antibodies with ACE2-like catalytic activity. The ACE2-like catalytic activity of these mAbs was not inhibited by MLN-4760, a compound that inhibits native human ACE2 catalytic activity, nor by EDTA, unlike native ACE2, a Zinc metalloprotease, but was inhibited by an overlapping pool of spike peptides. Enzyme kinetic studies showed that the mAbs had substantially lower Vmax and\n                  <jats:italic>Km<\/jats:italic>\n                  values than native ACE2. The data therefore suggested that the antibodies cleave ACE2 substrate via a different mechanism than native ACE2. The identification of specific mAbs with ACE2-like catalytic activity supports the hypothesis that antibodies induced by SARS-CoV-2 infection could help mediate the pathogenesis of COVID-19 and LC, and more generally, the hypothesis that catalytic antibodies induced by infectious agents can contribute to disease pathogenesis.\n                <\/jats:p>","DOI":"10.64898\/2026.02.02.703244","type":"posted-content","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:10:14Z","timestamp":1770318614000},"source":"Crossref","is-referenced-by-count":0,"title":["ACE-2-like Enzymatic Activity in Anti-SARS-CoV-2 Spike Protein Monoclonal Antibodies"],"prefix":"10.64898","author":[{"given":"Yufeng","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Mehl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"No","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Livingston","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Sebastian","family":"Quintero Barbosa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Precision Antibody, 9130 Red Branch Rd., Suite X Columbia, Maryland 21045, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginette","family":"Serrero","sequence":"additional","affiliation":[{"name":"Precision Antibody, 9130 Red Branch Rd., Suite X Columbia, Maryland 21045, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela Schoppee","family":"Bortz","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"James E","family":"Crowe","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Seattle, WA 98109, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D","family":"Ho","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T","family":"Yin","sequence":"additional","affiliation":[{"name":"Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Tan","sequence":"additional","affiliation":[{"name":"Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-9260","authenticated-orcid":false,"given":"Steven L","family":"Zeichner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042706000484000_2026.02.02.703244v3.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00904-7"},{"key":"2026042706000484000_2026.02.02.703244v3.2","doi-asserted-by":"crossref","first-page":"1117464","DOI":"10.3389\/fimmu.2023.1117464","article-title":"Long COVID: a review and proposed visualization of the complexity of long COVID","volume":"14","year":"2023","journal-title":"Frontiers in immunology"},{"key":"2026042706000484000_2026.02.02.703244v3.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00846-2"},{"key":"2026042706000484000_2026.02.02.703244v3.4","doi-asserted-by":"crossref","unstructured":"Adjaye-Gbewonyo D , Vahratian A , Perrine CG , Bertolli J. 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