Inhibitory effects of toothpaste and mouthwash ingredients on SARS-CoV-2 infection in vitro

ABSTRACT

Background and Aim: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Recently, some reports indicate that the severity of COVID-19 is associated with periodontal disease. SARS-CoV-2 host cell entry is mediated by viral spike protein binding to the host angiotensinconverting enzyme 2 (ACE2) and its cleavage by transmembrane protease serine 2 (TMPRSS2). ACE2 and TMPRSS2 are expressed in the oral cavity including periodontal pocket epithelium, tongue and saliva glands. Therefore, we hypothesized that inhibiting these two factors may prevent SARS-CoV-2 infections. This study aimed to investigate the inhibitory effects of general ingredients in commercially available toothpaste and mouthwash on SARS-CoV-2 infection. Methods: We evaluated the effects of 30 toothpaste and mouthwash ingredients on the SARS-CoV-2 spike protein-ACE2 interaction and TMPRSS2 protease activity using enzyme-linked immunosorbent assay and an in vitro enzyme activity assay, respectively. We also investigated whether the ingredients were in the presence of saliva. In addition, the binding state of each ingredient to the inhibitor-binding site of ACE2 or TMPRSS2 was evaluated by molecular docking simulation to understand the mechanisms involved. Results: Sodium tetradecene sulfonate, sodium N-lauroyl-N-methyltaurate, sodium N-lauroylsarcosinate, sodium dodecyl sulfate, and copper gluconate inhibited both spike protein-ACE2 interaction and TMPRSS2 activity. Furthermore, these ingredients also showed inhibitory effects on both spike protein-ACE2 interaction and TMPRRS2 activity in the presence of saliva. Molecular docking simulations suggested that these ingredients could bind to the inhibitor-binding site of ACE2. Conclusions: Our findings suggest that five ingredients in commercial toothpaste and mouthwash could inhibit the entry points of SARSCoV- 2 and could help to prevent SARS-CoV-2 infection.