The inhibitory effects of toothpaste and mouthwash ingredients on the interaction between the SARS-CoV-2 spike protein and ACE2, and the protease activity of TMPRSS2 in vitro.

SARS-CoV-2 enters host cells when the viral spike protein is cleaved by transmembrane protease serine 2 (TMPRSS2) after binding to the host angiotensin-converting enzyme 2 (ACE2). Since ACE2 and TMPRSS2 are expressed in the tongue and gingival mucosa, the oral cavity is a potential entry point for SARS-CoV-2. This study evaluated the inhibitory effects of general ingredients of toothpastes and mouthwashes on the spike protein-ACE2 interaction and the TMPRSS2 protease activity using an in vitro assay. Both assays detected inhibitory effects of sodium tetradecene sulfonate, sodium N-lauroyl-N-methyltaurate, sodium N-lauroylsarcosinate, sodium dodecyl sulfate, and copper gluconate. Molecular docking simulations suggested that these ingredients could bind to inhibitor-binding site of ACE2. Furthermore, tranexamic acid exerted inhibitory effects on TMPRSS2 protease activity. Our findings suggest that these toothpaste and mouthwash ingredients could help prevent SARS-CoV-2 infection.
Competing Interests: We have read the journal‘s policy and the authors of this manuscript have the following competing interests: R Tateyama-Makino, M Abe-Yutori, T Iwamoto, K Tsutsumi, S Morishita, K Kurita, Y Yamamoto, and E Nishinaga are employees of the Lion Corporation (Tokyo, Japan). M Tsuji is a President of the Institute of Molecular Function (Saitama, Japan). Molecular docking simulation was performed by the Institute of Molecular Function under a consignment from the Lion Corporation. K Tsukinoki has received fees for technical guidance from the Lion Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.