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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.

Adlay has been used as a traditional Chinese medicine and nutrient for its beneficial effects on bowel movements and skin care. This study examined the effect of enzymatic degradation product of adlay, “Super Hatomugi” (SPH) on human skin and the intestinal flora in a randomized, double-blind placebo-controlled study. The subjects were divided into three groups: 500 mg SPH, 1000 mg SPH, and placebo, taken daily for 4 weeks. Hematological and skin condition examinations as well as an analysis of intestinal flora were performed 2 weeks before and 10 weeks after the start of the SPH intake. Skin condition was improved by SPH intake as revealed by a reduction in the number of nucleated epidermal cells. In addition, an increase in the fecal population of Bacteroidetes followed the SPH intake. These results show the possibility that SPH improves the skin condition and changes the proportions of intestinal flora.