Oral Mucosa Could Be an Infectious Target of SARS-CoV-2

Okui, Tatsuo; Matsuda, Yuichi; Karino, Masaaki; Hideshima, Katsumi; Kanno, Takahiro

doi:10.3390/healthcare9081068

Cited by 22 publications

(26 citation statements)

References 24 publications

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“…This would lead to subsequent cytokine response of cells of oral cavity of individuals with hyperglycemia. This observation is in agreement with the fact that hyperglycemia is a co-morbidity in SARS-CoV2 viral infection [41][42][43] and the virus gains entry into the host cells through cells of the nose and oral cavity [44] which express ACE2 and TMPRSS2.…”

Section: Mhct08-e Grown In High Glucose Medium Showed Increased Ace2 ...supporting

confidence: 88%

Recombinant Human ACE2-Fc : A promising therapy for SARS-CoV2 infection

P.K

Shandil

Suresh

et al. 2022

Preprint

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SARS-CoV2 entry is mediated by binding of viral spike-protein(S) to the transmembrane Angiotensin-Converting Enzyme-2 (ACE2) of the host cell. Thus, to prevent transmission of disease, strategies to abrogate the interaction are important. However, ACE2 cannot be blocked since its normal function is to convert the Angiotensin II peptide to Angiotensin(1-7) to reduce hypertension. This work reports a recombinant cell line secreting soluble ACE2-ectopic domain (MFcS2), modified to increase binding and production efficacy and fused to human immunoglobulin-Fc. While maintaining its enzymatic activity, the molecule trapped and neutralized SARS CoV2 virus in vitro with an IC50 of 64 nM. In vivo, with no pathology in the vital organs, it inhibited the viral load in lungs in SARS-CoV2 infected Golden-Syrian-hamster. The Intravenous pharmacokinetic profiling of MFcS2 in hamster at a dose of 5 mg/Kg presented a maximum serum concentration of 23.45 microgram/mL with a half-life of 29.5 hrs. These results suggest that MFcS2 could be used as an effective decoy based therapeutic strategy to treat COVID19. This work also reports usage of a novel oral-cancer cell line as in vitro model of SARS-Cov2 infection, validated by over expressing viral-defence pathways upon RNA-seq analysis and over-expression of ACE2 and TMPRSS upon growth in hyperglycaemic condition.

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Section: Mhct08-e Grown In High Glucose Medium Showed Increased Ace2 ...supporting

confidence: 88%

Recombinant Human ACE2-Fc : A promising therapy for SARS-CoV2 infection

P.K

Shandil

Suresh

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Since the blockage of SARS‐CoV‐2 cell entry in HEK293T‐ACE2 and virus‐cell fusion assay in CHO‐K1 cells could also be due to the potential toxicity associated with the ORs, we next evaluated the potential side effect of the ORs by measuring the release of LDH—an enzyme, which is an indicator of cellular toxicity (Okui et al, 2021 ). In this experiment, we tested the impact of both the ORs separately on CHO‐K1 and HEK293T‐ACE2 cells using multiple dosages and the two critical time points (15 min and 48 h).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to ACE‐2, multiple other cell surface receptors and co‐receptors have also been proposed to support SARS‐CoV‐2 entry (Gadanec et al, 2021 ; Sigrist et al, 2020 ; Tiwari, Beer, et al, 2020 ; Tiwari, Tandon, et al, 2020 ). The ACE2 receptors are highly expressed in nasopharyngeal tissues and the oral cavity (Okui et al, 2021 ; Sawa et al, 2021 ; Xu et al, 2020 ; Zhong et al, 2020 ). Interestingly, the expression levels of ACE2 receptors vary depending on age, gender, and certain predispositions (Drozdzik & Drozdzik, 2022 ; Okui et al, 2021 ; Peng et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…The ACE2 receptors are highly expressed in nasopharyngeal tissues and the oral cavity (Okui et al, 2021 ; Sawa et al, 2021 ; Xu et al, 2020 ; Zhong et al, 2020 ). Interestingly, the expression levels of ACE2 receptors vary depending on age, gender, and certain predispositions (Drozdzik & Drozdzik, 2022 ; Okui et al, 2021 ; Peng et al, 2021 ). For instance, an increased expression of ACE2 receptors has been reported in the population with severe smokers, chronic obstructive pulmonary disease (COPD), diabetes, obesity, and Crohn's disease (Burgueno et al, 2020 ; Drucker, 2021 ; Yao et al, 2020 ), making compromised individuals with the above conditions at risk for SARS‐CoV‐2 infection.…”

Section: Introductionmentioning

confidence: 99%

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Significance of chlorine‐dioxide‐based oral rinses in preventing SARS‐CoV‐2 cell entry

et al. 2022

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Objective This work aims to determine the efficacy of preprocedural oral rinsing with chlorine dioxide solutions to minimize the risk of coronavirus disease 2019 (COVID‐19) transmission during high‐risk dental procedures. Methods The antiviral activity of chlorine‐dioxide‐based oral rinse (OR) solutions was tested by pre‐incubating with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pseudovirus in a dosage‐dependent manner before transducing to human embryonic kidney epithelial (HEK293T‐ACE2) cells, which stably expresses ACE‐2 receptor. Viral entry was determined by measuring luciferase activity using a luminescence microplate reader. In the cell‐to‐cell fusion assay, effector Chinese hamster ovary (CHO‐K1) cells co‐expressing spike glycoprotein of SARS‐CoV‐2 and T7 RNA polymerase were pre‐incubated with the ORs before co‐culturing with the target CHO‐K1 cells co‐expressing human ACE2 receptor and luciferase gene. The luciferase signal was quantified 24 h after mixing the cells. Surface expression of SARS‐CoV‐2 spike glycoprotein and ACE‐2 receptor was confirmed using direct fluorescent imaging and quantitative cell‐ELISA. Finally, dosage‐dependent cytotoxic effects of ORs were evaluated at two different time points. Results A dosage‐dependent antiviral effect of the ORs was observed against SARS‐CoV‐2 cell entry and spike glycoprotein mediated cell‐to‐cell fusion. This demonstrates that ORs can be useful as a preprocedural step to reduce viral infectivity. Conclusions Chlorine‐dioxide‐based ORs have a potential benefit for reducing SARS‐CoV‐2 entry and spread.

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“…Okui et al confirmed ACE2 immunolocalization in gingival cells collected from the gingival sulcus (and quantified to the same level as the tongue, which was formerly considered as one on the main SARS-CoV-2 entry routes, along with the salivary glands). The expression level of ACE2 in the keratinized mucosa of the palate was documented to be very mild [9].…”

Section: Oral Cavity As the Sars-cov-2 Entry Gateway 21 Oral Mucosamentioning

confidence: 99%

Oral Pathology in COVID-19 and SARS-CoV-2 Infection—Molecular Aspects

Droździk

2022

IJMS

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This review article was designed to evaluate the existing evidence related to the molecular processes of SARS-CoV-2 infection in the oral cavity. The World Health Organization stated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission is produced by respiratory droplets and aerosols from the oral cavity of infected patients. The oral cavity structures, keratinized and non-keratinized mucosa, and salivary glands’ epithelia express SARS-CoV-2 entry and transmission factors, especially angiotensin converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Replication of the virus in cells leads to local and systemic infection spread, and cellular damage is associated with clinical signs and symptoms of the disease in the oral cavity. Saliva, both the cellular and acellular fractions, holds the virus particles and contributes to COVID-19 transmission. The review also presents information about the factors modifying SARS-CoV-2 infection potential and possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the oral cavity. The PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, COVID-19, oral virus infection, saliva, crevicular fluid, salivary gland, tongue, oral mucosa, periodontium, gingiva, dental pulp, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and related words in relevant publications up to 28 December 2021. Data extraction and quality evaluation of the articles were performed by two reviewers, and 63 articles were included in the final review.

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Oral Mucosa Could Be an Infectious Target of SARS-CoV-2

Cited by 22 publications

References 24 publications

Recombinant Human ACE2-Fc : A promising therapy for SARS-CoV2 infection

Recombinant Human ACE2-Fc : A promising therapy for SARS-CoV2 infection

Significance of chlorine‐dioxide‐based oral rinses in preventing SARS‐CoV‐2 cell entry

Oral Pathology in COVID-19 and SARS-CoV-2 Infection—Molecular Aspects

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