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J Biochem 2022[Sep]; 172 (4): 205-216 PMID35792074show ga
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 epsilon-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.
|*Angiotensin-Converting Enzyme 2[MESH]
|*COVID-19[MESH]
|Histones/metabolism[MESH]
|Humans[MESH]
|Leukocyte Elastase/metabolism[MESH]
|Peptidyl-Dipeptidase A/metabolism[MESH]
|Polylysine/metabolism[MESH]
|Protein Binding[MESH]
|SARS-CoV-2[MESH]
|Salivary Proteins and Peptides/metabolism/pharmacology[MESH]
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J+Biochem 2022 ; 172 (4): 205-216
