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Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry

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...

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Autores principales: Yoshizato, Katsutoshi, Taira, Toshio, Sato-Matsubara, Misako, Sekiguchi, Shizuko, Yabunaka, Yoriko, Kira, Yukimi, Ohashi, Tetsu, Daikoku, Atsuko, Ofusa, Ken, Kadono, Chiho, Oikawa, Daisuke, Matsubara, Tsutomu, Nakagama, Yu, Kido, Yasutoshi, Tokunaga, Fuminori, Ikeda, Kazuo, Kaneko, Akira, Kawada, Norifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278198/
https://www.ncbi.nlm.nih.gov/pubmed/35792074
http://dx.doi.org/10.1093/jb/mvac054
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author Yoshizato, Katsutoshi
Taira, Toshio
Sato-Matsubara, Misako
Sekiguchi, Shizuko
Yabunaka, Yoriko
Kira, Yukimi
Ohashi, Tetsu
Daikoku, Atsuko
Ofusa, Ken
Kadono, Chiho
Oikawa, Daisuke
Matsubara, Tsutomu
Nakagama, Yu
Kido, Yasutoshi
Tokunaga, Fuminori
Ikeda, Kazuo
Kaneko, Akira
Kawada, Norifumi
author_facet Yoshizato, Katsutoshi
Taira, Toshio
Sato-Matsubara, Misako
Sekiguchi, Shizuko
Yabunaka, Yoriko
Kira, Yukimi
Ohashi, Tetsu
Daikoku, Atsuko
Ofusa, Ken
Kadono, Chiho
Oikawa, Daisuke
Matsubara, Tsutomu
Nakagama, Yu
Kido, Yasutoshi
Tokunaga, Fuminori
Ikeda, Kazuo
Kaneko, Akira
Kawada, Norifumi
author_sort Yoshizato, Katsutoshi
collection PubMed
description 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 ε-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.
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spelling pubmed-92781982022-07-18 Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry Yoshizato, Katsutoshi Taira, Toshio Sato-Matsubara, Misako Sekiguchi, Shizuko Yabunaka, Yoriko Kira, Yukimi Ohashi, Tetsu Daikoku, Atsuko Ofusa, Ken Kadono, Chiho Oikawa, Daisuke Matsubara, Tsutomu Nakagama, Yu Kido, Yasutoshi Tokunaga, Fuminori Ikeda, Kazuo Kaneko, Akira Kawada, Norifumi J Biochem Regular Paper 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 ε-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. Oxford University Press 2022-07-06 /pmc/articles/PMC9278198/ /pubmed/35792074 http://dx.doi.org/10.1093/jb/mvac054 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Japanese Biochemical Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Paper
Yoshizato, Katsutoshi
Taira, Toshio
Sato-Matsubara, Misako
Sekiguchi, Shizuko
Yabunaka, Yoriko
Kira, Yukimi
Ohashi, Tetsu
Daikoku, Atsuko
Ofusa, Ken
Kadono, Chiho
Oikawa, Daisuke
Matsubara, Tsutomu
Nakagama, Yu
Kido, Yasutoshi
Tokunaga, Fuminori
Ikeda, Kazuo
Kaneko, Akira
Kawada, Norifumi
Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title_full Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title_fullStr Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title_full_unstemmed Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title_short Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry
title_sort cloaking the ace2 receptor with salivary cationic proteins inhibits sars-cov-2 entry
topic Regular Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278198/
https://www.ncbi.nlm.nih.gov/pubmed/35792074
http://dx.doi.org/10.1093/jb/mvac054
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