{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:04:57Z","timestamp":1789761897010,"version":"4.0.1"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100008476","name":"University of California, Irvine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1) and human ACE2 receptor is essential for viral entry into host epithelial cells and a key target for drug discovery. Here, we describe the evolution of a threomer, a base-modified version of threose nucleic acid (TNA), that binds to the S1 protein and inhibits its interaction with ACE2. The aptamer was isolated by in vitro selection using a DNA display strategy that linked each TNA molecule to its encoding double-stranded DNA template. Following iterative cycles of selection and amplification, lead candidates were identified by parallelized screening of individual variants in hydrogel particles. The top-performing hit exhibits low nanomolar affinity to the S1 protein and inhibits formation of the S1\u2212ACE2 complex. Together, this work establishes threomers as an emerging platform for inhibiting protein\u2212protein interactions in therapeutic targets.<\/jats:p>","DOI":"10.1021\/acssynbio.6c00516","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:02:22Z","timestamp":1786629742000},"page":"3833-3840","source":"Crossref","is-referenced-by-count":0,"title":["Threomer Inhibition of S1\u2212ACE2 Binding"],"prefix":"10.1021","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-0596","authenticated-orcid":true,"given":"Adriana","family":"Lozoya-Colinas","sequence":"first","affiliation":[{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4471-7649","authenticated-orcid":true,"given":"Joy J.","family":"Lee","sequence":"additional","affiliation":[{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4551-9350","authenticated-orcid":true,"given":"Nandini","family":"Kundu","sequence":"additional","affiliation":[{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-0303","authenticated-orcid":true,"given":"Erica M.","family":"Lee","sequence":"additional","affiliation":[{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1393-135X","authenticated-orcid":true,"given":"John C.","family":"Chaput","sequence":"additional","affiliation":[{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]},{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]},{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]},{"name":"University of California , , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026091815071346900_cit1","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"2026091815071346900_cit2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"2026091815071346900_cit3","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1146\/annurev.biochem.68.1.611","article-title":"In vitro selection of functional nucleic acids","volume":"68","author":"Wilson","year":"1999","journal-title":"Annu. 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