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

PLoS One. 2021 Sep 17;16(9):e0257705. doi: 10.1371/journal.pone.0257705. eCollection 2021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / immunology
  • COVID-19 / prevention & control*
  • Humans
  • Mouthwashes / pharmacology*
  • Oral Hygiene / methods*
  • SARS-CoV-2 / drug effects*
  • Serine Endopeptidases / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Toothpastes / pharmacology*
  • Virus Internalization / drug effects*

Substances

  • Mouthwashes
  • Spike Glycoprotein, Coronavirus
  • Toothpastes
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Grants and funding

This work was fully funded by Lion Corporation (https://www.lion.co.jp/en/). R Tateyama-Makino, M Abe-Yutori, T Iwamoto, K Tsutsumi, S Morishita, K Kurita, Y Yamamoto, and E Nishinaga are employees of Lion Corporation. The Lion Corporation provided support in the form of salaries for authors R Tateyama-Makino, M Abe-Yutori, T Iwamoto, K Tsutsumi, S Morishita, K Kurita, Y Yamamoto, and E Nishinaga. 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section.