Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva
A team of international scientists has demonstrated the usefulness of
cetylpyridinium chloride-containing mouthwashes in inhibiting severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) and reducing the risk of
viral transmission. The study is currently available on the bioRxiv* preprint server.
Cetylpyridinium chloride Mouthwash (Amazon
Due to the presence of angiotensin-converting enzyme 2 (ACE2) in the oral
gingival epithelium and salivary glands, the human oral cavity may act as a
reservoir for SARS-CoV-2. The ACE2 present on the host cell membrane acts as
the primary entry receptor for SARS-CoV-2. Evidence indicates that the saliva
of SARS-CoV-2-infected individuals contains high amounts of viral RNA and that
aerosols formed from the saliva can act as a potential vector for viral
Several health organizations have advised using mouthwashes during dentistry
procedures as a measure to inhibit SARS-CoV-2 transmission. Bioactive
ingredients present in mouthwashes, including dequalinium chloride,
benzalkonium chloride, cetylpyridinium chloride (CPC) and chlorhexidine, have
been found to inhibit pathogens by charge-mediated attraction and
destabilization of the lipid envelope.
In the current study, the scientists have investigated in vitro antiviral efficacy of mouthwashes containing cetylpyridinium chloride (0.07%) or
chlorhexidine digluconate (0.2%) against SARS-CoV-2 and its variants,
including B.1.1.7, B.1.351, and P1. Moreover, in a separate set of in vitro experiments, they have determined the antiviral efficacy of
cetylpyridinium chloride-containing mouthwash in the presence of human saliva
to investigate whether salivary components can deactivate the active agent.
To measure viral titers, they conducted a plaque assay after 30 seconds of
mouthwash exposure. They tested different mouthwash formulations including
cetylpyridinium chloride with flavor, cetylpyridinium chloride with flavor and
herbal mix, and chlorhexidine digluconate with flavor. As positive and
negative controls, they have used 70% ethanol and water, respectively.
The plaque assay findings revealed that both formulations of cetylpyridinium
chloride-containing mouthwash are capable of inhibiting SARS-CoV-2 by 99.99%.
After 30 seconds of exposure to these formulations resulted in a viral titer
value below the detection limit. In contrast, chlorhexidine
digluconate-containing mouthwash showed significantly lower efficacy in
Furthermore, both formulations of cetylpyridinium chloride-containing
mouthwash exhibited high efficacy in reducing the titers of B.1.1.7, B.1.351,
and P1 below the detection limit. However, no such reduction was observed for
chlorhexidine digluconate-containing mouthwash.
Functionality of mouthwash in presence of human saliva
Scientists first tested whether mouthwash formulations remain effective in the
presence of saliva by testing the endogenous antiviral efficacy of saliva
against SARS-CoV-2. However, they could not observe any reduction in viral
titers after 5 minutes of exposure to saliva. This indicates that human saliva
alone does not have any intrinsic antiviral activity.
Afterward, they tested whether salivary components can alter the
anti-SARS-CoV-2 efficacy of cetylpyridinium chloride. The findings revealed
that cetylpyridinium chloride-containing mouthwash is capable of completely
inhibiting the virus even in presence of saliva.
Irradiated human saliva has no effect upon the viral titer of
SARS-CoV-2 as compared to the water control after incubation with
inoculum for 5 minutes. Neat saliva had a ratio of 8 parts water to
1-part irradiated human saliva to 1-part virus inoculum, while dilute
saliva had a ratio 9 parts irradiated human saliva to 1-part virus
inoculum (A). Human saliva does not inhibit the antiviral activity of
mouthwash formulas proven to reduce the titer of SARS-CoV-2 (B). MW-B
was able to reduce viral titer to below the LODboth in the presence of
irradiated human saliva and without. Human saliva was added in a ratio
of 8 parts MW-B to 1-part irradiated human saliva to 1-part virus
inoculum. Limit of detection (LOD) (2.0log10 PFU/mL) is shown across
both graphs with a dotted red line. Error bars represent standard
deviation, while red dots are experimental data values and blue dots
The study highlights the potential of cetylpyridinium
chloride-containing mouthwashes in inhibiting SARS-CoV-2 and its
variants. Regular use of such low-cost mouthwashes as a good oral
hygiene practice could potentially reduce the risk of viral transmission
to others, as well as through the respiratory tract of an infected
Anti-SARS-CoV-2 effectiveness of cetylpyridinium chloride-containing
mouthwashes has also been reported in other studies. In addition, human
clinical trials are reporting that rinsing the oral cavity with
cetylpyridinium chloride-containing mouthwash can effectively reduce the
amount of SARS-CoV-2 in saliva for several hours.
Some recent studies have shown that plaque build-up in the oral cavity
due to poor hygiene, and subsequent gum infection can increase the risk
of viral entry via the oral gingival sulcus and periodontal pockets,
leading to respiratory and systemic SARS-CoV-2 infection. Based on the
current study findings, such risk can be reduced by regular use of
cetylpyridinium chloride-containing mouthwashes.
The effectiveness of mouthwash against SARS-CoV-2 infection: A review of scientific and clinical evidence
Background: The COVID-19 pandemic, caused by the spread of SARS-CoV-2 infection that is mainly through the airborne transmission, is a worldwide health concern. This review seeks to assess the potential effectiveness of mouthwash in reducing the oropharyngeal load of SARS-CoV-2 based on the available evidence.
Methods: Articles related to mouthwash and COVID-19 in PubMed were electronically searched in July, 2021. After manually excluding articles lacking sufficient scientific evidence or validation processes, those with inaccessible online full text, those that did not test the effectiveness of mouthwash against SARS-CoV-2, and those not written in English, 17 original and 13 review articles were chosen for this review.
Results: The eligible articles revealed that the main virucidal mechanism of mouthwash was via interactions with the viral envelope. Povidone-iodine (PVP-I), cetylpyridinium chloride (CPC), and essential oils with ethanol showed virucidal effects on SARS-CoV-2 in vitro, potentially by interfering with the viral envelope. A few clinical studies demonstrated that PVP-I, CPC, hydrogen peroxide, and chlorhexidine reduced the oropharyngeal load of SARS-CoV-2.
Conclusion: Although the available evidence is limited, mouthwash containing PVP-I or CPC shows potential for reducing the oropharyngeal load of SARS-CoV-2 and thus may present a risk-mitigation strategy for COVID-19 patients.
Cetylpyridinium chloride Dangers
Cetylpyridinium chloride in mouthwash has been misattributed as a cause of oral cancer in the past, but research has not shown it to link to any form of cancer – no more than any other compound used in mouthwash. The risks of CPC are minor; it is only toxic in large doses (1 gram or more of pure CPC, ingested) and as an antimicrobial spray on food, it is far more helpful than harmful. Frequent and heavy use of a CPC-based mouthwash or toothpaste can bring side effects, however. Frequent use of CPC-based oral hygiene products can cause minor brown staining on teeth, a slight burning sensation in the gums and the products have been found to promote the formation of calculus (also known as tartar) on some users' teeth. None of these side effects are particularly harmful, but they should be considered.
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