Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2

Takeda, Ryo; Sawa, Hirofumi; Sasaki, Michihito; Orba, Yasuko; Maishi, Nako; Tsumita, Takuya; Ushijima, Natsumi; Hida, Yasuhiro; Sano, Hidehiko; Kitagawa, Yoshimasa; Hida, Kyoko

doi:10.1038/s41598-022-18367-6

Cited by 25 publications

(23 citation statements)

References 32 publications

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“…60 This antiviral efficacy seems also to be observed across different viral strains and in saliva, while the mechanism is occurring without disruption of the viral particles and that the denaturing effect of the spike protein may have a role. 61 Cetylpyridinium chloride has also been tested in Caco-2 cells (IC 50 = 0.62 μM). 23 Several clinical trials have also indicated efficacy against SARS-CoV-2.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Others have described the SARS-CoV-2 virucidal activity of this molecule in Vero cells upon short exposure and that it interfered with the spike and ACE2 interaction . This antiviral efficacy seems also to be observed across different viral strains and in saliva, while the mechanism is occurring without disruption of the viral particles and that the denaturing effect of the spike protein may have a role . Cetylpyridinium chloride has also been tested in Caco-2 cells (IC 50 = 0.62 μM) .…”

Section: Discussionmentioning

confidence: 99%

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Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2

et al. 2023

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There are very few small-molecule antivirals for SARS-CoV-2 that are either currently approved (or emergency authorized) in the US or globally, including remdesivir, molnupiravir, and paxlovid. The increasing number of SARS-CoV-2 variants that have appeared since the outbreak began over three years ago raises the need for continual development of updated vaccines and orally available antivirals in order to fully protect or treat the population. The viral main protease (Mpro) and the papain-like protease (PLpro) are key for viral replication; therefore, they represent valuable targets for antiviral therapy. We herein describe an in vitro screen performed using the 2560 compounds from the Microsource Spectrum library against Mpro and PLpro in an attempt to identify additional small-molecule hits that could be repurposed for SARS-CoV-2. We subsequently identified 2 hits for Mpro and 8 hits for PLpro. One of these hits was the quaternary ammonium compound cetylpyridinium chloride with dual activity (IC50 = 2.72 ± 0.09 μM for PLpro and IC50 = 7.25 ± 0.15 μM for Mpro). A second inhibitor of PLpro was the selective estrogen receptor modulator raloxifene (IC50 = 3.28 ± 0.29 μM for PLpro and IC50 = 42.8 ± 6.7 μM for Mpro). We additionally tested several kinase inhibitors and identified olmutinib (IC50 = 0.54 ± 0.04 μM), bosutinib (IC50 = 4.23 ± 0.28 μM), crizotinib (IC50 = 3.81 ± 0.04 μM), and dacominitinib (IC50 = IC50 3.33 ± 0.06 μM) as PLpro inhibitors for the first time. In some cases, these molecules have also been tested by others for antiviral activity for this virus, or we have used Calu-3 cells infected with SARS-CoV-2. The results suggest that approved drugs can be identified with promising activity against these proteases, and in several cases we or others have validated their antiviral activity. The additional identification of known kinase inhibitors as molecules targeting PLpro may provide new repurposing opportunities or starting points for chemical optimization.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2

et al. 2023

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“…46 Newer research suggests that CPC disrupts the envelope in high concentrations (50%-75%), whereas low concentrations (1%-4%) of CPC denature virus proteins. 47 CPC is tasteless and odourless compared with CHX and PVI. Oral retention of CPC is higher than CHX immediately after mouthwash but are significantly lower than CHX 4 h after rinsing and onwards.…”

Section: Et Y L P Y R I Di N Iu M Ch Lor Idementioning

confidence: 95%

Commonly used dental mouthwashes and SARS‐CoV‐2—The road to what we know today

Vigen

Skoglund

2023

Oral Surgery

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The aim of this brief overview is to give clinicians a background for assessing publications presenting in vivo human clinical trials regarding the effect of common dental mouthwashes on SARS-CoV-2 virus. It explains how the effects of oral mouthwashes on oro-nasally transmitted infectious virus was assessed in the early phase of the Covid-19 pandemic. The method of virus quantification including effect measures and factors, trial design that may cause flaws in the effect estimates presented in publications are explained. The status of in vivo human clinical trials regarding the anti-virucidal effect of sodium lauryl sulfate, povidone-iodine, chlorhexidine, hydrogen peroxide and cetylpyridinium chloride is presented from the few systematic reviews available at this time.

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“…The combined use of CPC or CHA with other disinfectants has been reported, e.g., nystatin [ 17 ], fluconazole [ 18 ], and chlorhexidine digluconate [ 19 ], which exhibited lower minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) against target bacteria or fungi than using either of them alone. Besides combining with other disinfectants, these two drugs have also been used in combination to eliminate living bacteria on in situ collected biofilms and virus [ 20 , 21 ]. However, these reports only focused on the disinfection effect on a single type of pathogenic microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Combination of Cetylpyridinium Chloride and Chlorhexidine Acetate: A Promising Candidate for Rapid Killing of Gram-Positive/Gram-Negative Bacteria and Fungi

Zhu

Zhang

et al. 2023

Curr Microbiol

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Combined use of the present antimicrobial drugs has been proved to be an alternative approach for antimicrobial agents’ development since the co-existed of the drugs working in different mechanism have been demonstrated potentially enhance their antimicrobial activity. In this work, antibacterial and antifungal activity of the cetylpyridinium chloride (CPC)/chlorhexidine acetate (CHA) combination was evaluated for the first time, while a universal concentration for the rapid killing of gram-positive/gram-negative bacteria and fungi was also proposed. The minimum inhibitory concentrations (MIC) of CPC and CHA used alone or in combination were first measured, showing that the combined treatment decreased the MIC against tested gram-positive/gram-negative bacteria and fungi to 1/8–1/2. Growth curve assays demonstrated CPC and CHA had dynamic combined effects against the tested microorganisms at the concentration equal to MIC. Besides, combined use of these two drugs could also enhance their biocidal activity, which was illustrated by fluorescence microscopy and SEM images, as well as soluble protein measurement. More importantly, in vitro acute eye and skin irritation tests showed short-term contact with CPC/CHA combination would not cause any damage to mammalian mucosa and skin. In a word, CPC/CHA combination exhibited broad-spectrum antibacterial and antifungal activity against tested gram-positive/gram-negative bacteria and fungi while without any acute irritation to mammalian mucosa and skin, providing a new perspective on the selection of personal disinfectants. Supplementary Information The online version contains supplementary material available at 10.1007/s00284-023-03198-z.

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Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2

Cited by 25 publications

References 32 publications

Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2

Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2

Commonly used dental mouthwashes and SARS‐CoV‐2—The road to what we know today

Combination of Cetylpyridinium Chloride and Chlorhexidine Acetate: A Promising Candidate for Rapid Killing of Gram-Positive/Gram-Negative Bacteria and Fungi

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Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2

Cited by 25 publications

References 32 publications

Discovery of PLpro and Mpro Inhibitors for SARS-CoV-2

Discovery of PLpro and Mpro Inhibitors for SARS-CoV-2

Commonly used dental mouthwashes and SARS‐CoV‐2—The road to what we know today

Combination of Cetylpyridinium Chloride and Chlorhexidine Acetate: A Promising Candidate for Rapid Killing of Gram-Positive/Gram-Negative Bacteria and Fungi

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Product

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Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2

Discovery of PL^pro and M^pro Inhibitors for SARS-CoV-2