Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry. (6th July 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of biochemistry. Volume 172:Number 4(2022)
• Page Start: 205
• Page End: 216
• Publication Date: 2022-07-06
• Subjects: SARS-CoV-2 spike protein -- saliva -- neutrophil elastase -- histone H2A -- angiotensin-converting enzyme 2; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Electronic journals; 572.05
• DOI: 10.1093/jb/mvac054
• Languages: English
• ISSNs: 0021-924X

Abstract

Abstract: 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. Graphical Abstract: