{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:45:16Z","timestamp":1771461916857,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GSK Japan Research Grant 2021","award":["ID:AS2021A000213086"],"award-info":[{"award-number":["ID:AS2021A000213086"]}]},{"name":"Osaka City University, Strategic Research Grant 2021 for top priority research","award":["OCU-SRG2021_TPR01"],"award-info":[{"award-number":["OCU-SRG2021_TPR01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Saliva contributes to the innate immune system, which suggests that it can prevent SARS-CoV-2 entry. We studied the ability of healthy salivary proteins to bind to angiotensin-converting enzyme 2 (ACE2) using biolayer interferometry and pull-down assays. Their effects on binding between the receptor-binding domain of the SARS-CoV-2 spike protein S1 (S1) and ACE2 were determined using an enzyme-linked immunosorbent assay. Saliva bound to ACE2 and disrupted the binding of S1 to ACE2 and four ACE2-binding salivary proteins were identified, including cationic histone H2A and neutrophil elastase, which inhibited the S1-ACE2 interaction. Calf thymus histone (ct-histone) also inhibited binding as effectively as histone H2A. The results of a cell-based infection assay indicated that ct-histone suppressed SARS-CoV-2 pseudoviral invasion into ACE2-expressing host cells. Manufactured polypeptides, such as \u03b5-poly-L-lysine, also disrupted S1-ACE2 binding, indicating the importance of the cationic properties of salivary proteins in ACE2 binding. Overall, we demonstrated that positively charged salivary proteins are a barrier against SARS-CoV-2 entry by cloaking the negatively charged surface of ACE2 and provided a view that the cationic polypeptides represent a preventative and therapeutic treatment against COVID-19.<\/jats:p>","DOI":"10.1093\/jb\/mvac054","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T10:37:01Z","timestamp":1657103821000},"page":"205-216","source":"Crossref","is-referenced-by-count":8,"title":["Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry"],"prefix":"10.1093","volume":"172","author":[{"given":"Katsutoshi","family":"Yoshizato","sequence":"first","affiliation":[{"name":"Osaka Metropolitan University Donated Laboratory for Synthetic Biology, Graduate School of Medicine, , Osaka 545-8585, Japan"},{"name":"Osaka Metropolitan University BioIntegrence Co., Graduate School of Medicine, , Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Taira","sequence":"additional","affiliation":[{"name":"Cosmo Bio Co., Ltd Sapporo Division, , Otaru, Hokkaido 047-0261, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misako","family":"Sato-Matsubara","sequence":"additional","affiliation":[{"name":"Osaka Metropolitan University Donated Laboratory for Synthetic Biology, Graduate School of Medicine, , Osaka 545-8585, Japan"},{"name":"Osaka Metropolitan University Department of Hepatology, Graduate School of Medicine, , Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizuko","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Cosmo Bio Co., Ltd Sapporo Division, , Otaru, Hokkaido 047-0261, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoriko","family":"Yabunaka","sequence":"additional","affiliation":[{"name":"Osaka Metropolitan University Department of Research Support Platform, Graduate School of Medicine, , Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukimi","family":"Kira","sequence":"additional","affiliation":[{"name":"Osaka Metropolitan University Department of Research Support Platform, Graduate School of Medicine, , Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsu","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Cosmo Bio Co., Ltd Sapporo Division, , Otaru, Hokkaido 047-0261, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuko","family":"Daikoku","sequence":"additional","affiliation":[{"name":"Osaka Metropolitan University Anatomy and Regenerative Biology, Graduate School of Medicine, , Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Ofusa","sequence":"additional","affiliation":[{"name":"IDEA Consultants, Inc. 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