{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:13:33Z","timestamp":1790817213638,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010799","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"F\u00e9d\u00e9ration pour la recherche m\u00e9dicale","award":["ANR 20 Flash Covid 19 \u2013 FRM program"],"award-info":[{"award-number":["ANR 20 Flash Covid 19 \u2013 FRM program"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The binding of the SARS-CoV-2 spike to angiotensin-converting enzyme 2 (ACE2) promotes virus entry into the cell. Targeting this interaction represents a promising strategy to generate antivirals. By screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal HEAT-like scaffold (named \u03b1Reps), we selected candidates recognizing the spike receptor binding domain (RBD). Two of them (F9 and C2) bind the RBD with affinities in the nM range, displaying neutralisation activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and recognizing distinct sites, F9 overlapping the ACE2 binding motif. The F9-C2 fusion protein and a trivalent \u03b1Rep form (C2-foldon) display 0.1 nM affinities and EC\n                    <jats:sub>50<\/jats:sub>\n                    of 8\u201318 nM for neutralization of SARS-CoV-2. In hamsters, F9-C2 instillation in the nasal cavity before or during infections effectively reduced the replication of a SARS-CoV-2 strain harbouring the D614G mutation in the nasal epithelium. Furthermore, F9-C2 and\/or C2-foldon effectively neutralized SARS-CoV-2 variants (including delta and omicron variants) with EC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 13 to 32 nM. With their high stability and their high potency against SARS-CoV-2 variants, \u03b1Reps provide a promising tool for SARS-CoV-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010799","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T13:48:13Z","timestamp":1662472093000},"page":"e1010799","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biosynthetic proteins targeting the SARS-CoV-2 spike as 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