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Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.

SUBMITTER: Sakaguchi W

PROVIDER: S-EPMC7503451 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

Sakaguchi Wakako W Kubota Nobuhisa N Shimizu Tomoko T Saruta Juri J Fuchida Shinya S Kawata Akira A Yamamoto Yuko Y Sugimoto Masahiro M Yakeishi Mayumi M Tsukinoki Keiichi K

International journal of molecular sciences 20200820 17

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratifi ...[more]

PMID: 32825469

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Project description:ObjectiveUsing a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva.MethodsThe potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva.ResultsA dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm2 delivered at irradiance less than 200 mW/cm2. A non-hazardous 425 nm light dose in this range (30 J/cm2 at 50 mW/cm2) was shown to inactivate SARS-CoV-2 in vitro in artificial saliva.ConclusionPreclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19.Clinical significanceThe process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.

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Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

Publications

Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity.

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