Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo.
Open accessAbstract
AbstractBackground: There is a continued need for strategies to prevent influenza. While cetylpyridinium chloride (CPC), a broad-spectrum antimicrobial agent, has an extensive antimicrobial spectrum, its ability to affect respiratory viruses has not been studied in detail.Objectives: Here, we evaluate the ability of CPC to disrupt influenza viruses in vitro and in vivo.Methods: The virucidal activity of CPC was evaluated against susceptible and oseltamivir- resistant strains of influenza viruses. The effective virucidal concentration (EC) of CPC was determined using a hemagglutination assay and tissue culture infective dose assay. The effect of CPC on viral envelope morphology and ultrastructure was evaluated using transmission electron microscopy (TEM). The ability of influenza virus to develop resistance was evaluated after multiple passaging in sub-inhibitory concentrations of CPC. Finally, the efficacy of CPC in formulation to prevent and treat influenza infection was evaluated using the PR8 murine influenza model.Results: The virucidal effect of CPC occurred within 10 minutes, with mean EC50 and EC2log ranging between 5 to 20 µg/mL, for most strains of influenza tested regardless of type and resistance to oseltamivir. Examinations using TEM showed that CPC disrupted the integrity of the viral envelope and its morphology. Influenza viruses demonstrated no resistance to CPC despite prolonged exposure. Treated mice exhibited significantly increased survival and maintained body weight compared to untreated mice.Conclusions: The antimicrobial agent CPC possesses virucidal activity against susceptible and resistant strains of influenza virus by targeting and disrupting the viral envelope. Substantial virucidal activity is seen even at very low concentrations of CPC without development of resistance. Moreover, CPC in formulation reduces influenza-associated mortality and morbidity in vivo.Keywords: Cetylpyridinium Chloride, CPC, Influenza, Respiratory tract illness, respiratory virus, quaternary ammonium compound
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0.05-0.1% CPC showed potent, rapid activity against MERS-CoV and influenza viruses.
“In addition, 0.05∼0.1% CPC showed potent, rapid activity against MERS-CoV (Shen et al., 2019) and influenza viruses (Popkin et al., 2017), however it’s activity against SARS-CoV-2 is currently unknown.”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Popkin et al., 2017
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Cites
Home visits: a strategy to improve newborn survival - Authors' reply
(2008) · Americanae (AECID Library) · doi:10.1016/s0140 · Cited by 22,524 · see citing works
Neutral red uptake assay for the estimation of cell viability/cytotoxicity
Repetto, G., del Peso, A., & Zurita, J. L. (2008) · Nature Protocols · doi:10.1038/nprot.2008.75 · Cited by 2,217 · see citing works
The annual impact of seasonal influenza in the US: Measuring disease burden and costs
Molinari, N., Ortega‐Sanchez, I. R., Messonnier, M. L., Thompson, W., WORTLEY, P. M., Weintraub, E., & Bridges, C. B. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.03.046 · Cited by 1,722 · see citing works
Cationic antiseptics: diversity of action under a common epithet
Gilbert, P., & Moore, L. E. (2005) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2005.02664.x · Cited by 1,168 · see citing works
Vaccines for preventing influenza in healthy adults
Jefferson, T., Pietrantonj, C. D., Rivetti, A., Bawazeer, G. A., Al‐Ansary, L. A., & Ferroni, E. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001269.pub4 · Cited by 898 · see citing works
Fiore, A. E., Fry, A. M., Shay, D. K., Gubareva, L. V., Bresee, J., & Uyeki, T. M. (2011) · PubMed · Cited by 761 · see citing works
Jacobs, S. E., Lamson, D. M., George, K. S., & Walsh, T. J. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00077-12 · Cited by 732 · see citing works
Viral and Bacterial Interactions in the Upper Respiratory Tract
Bosch, A. A. T. M., Biesbroek, G., Trzcinski, K., Sanders, E. A. M., & Bogaert, D. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003057 · Cited by 651 · see citing works
Harper, S. A., Bradley, J. S., Englund, J. A., File, T. M., Gravenstein, S., Hayden, F. G., McGeer, A. J., Neuzil, K. M., Pavia, A. T., Tapper, M. L., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/598513 · Cited by 647 · see citing works
Prevention and Control of Seasonal Influenza with Vaccines
Grohskopf, L. A., Sokolow, L. Z., Broder, K. R., Olsen, S. J., Karron, R. A., Jernigan, D. B., & Bresee, J. (2016) · MMWR Recommendations and Reports · doi:10.15585/mmwr.rr6505a1 · Cited by 597 · see citing works
Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children
Jefferson, T., Jones, M., Doshi, P., Mar, C. D., Heneghan, C. J., Hama, R., & Thompson, M. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008965.pub3 · Cited by 596 · see citing works
Cationic Antimicrobial Polymers and Their Assemblies
Carmona‐Ribeiro, A. M., & Carrasco, L. D. D. M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14059906 · Cited by 531 · see citing works
Kunisaki, K. M., & Janoff, E. N. (2009) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(09)70175-6 · Cited by 516 · see citing works
Bacterial target sites for biocide action
Maillard, J. (2002) · Journal of Applied Microbiology · doi:10.1046/j.1365-2672.92.5s1.3.x · Cited by 469 · see citing works
Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance
McKimm‐Breschkin, J. L. (2012) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12047 · Cited by 392 · see citing works
Hu, Y., Lu, S., Song, Z., Wang, W., Hao, P., Li, J., Zhang, X., Yen, H., Shi, B., Li, T., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61125-3 · Cited by 356 · see citing works
Influenza: Propagation, Quantification, and Storage
Szretter, K. J., Balish, A. L., & Katz, J. M. (2006) · Current Protocols in Microbiology · doi:10.1002/0471729256.mc15g01s3 · Cited by 296 · see citing works
Antiviral Drug Resistance: Mechanisms and Clinical Implications
Strasfeld, L. M., & Chou, S. (2010) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2010.01.001 · Cited by 253 · see citing works
Influenza A virus isolation, culture and identification
Eisfeld, A. J., Neumann, G., & Kawaoka, Y. (2014) · Nature Protocols · doi:10.1038/nprot.2014.180 · Cited by 246 · see citing works
Vaccines for preventing influenza in healthy adults
Demicheli, V., Jefferson, T., Al‐Ansary, L. A., Ferroni, E., Rivetti, A., & Pietrantonj, C. D. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001269.pub5 · Cited by 193 · see citing works
Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness — United States, February 2018
Flannery, B. L., Chung, J. R., Belongia, E. A., et al. (2018) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6706a2 · Cited by 179 · see citing works
Lu, P.-J., Santibanez, T. A., Williams, W. W., Zhang, J., Ding, H., Bryan, L. N., O’Halloran, A. C., Greby, S. M., Bridges, C. B., Graitcer, S. B., et al. (2013) · PubMed · Cited by 169 · see citing works
Pizzorno, A., Bouhy, X., Abed, Y., & Boivin, G. (2010) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiq010 · Cited by 157 · see citing works
Michiels, B., Puyenbroeck, K. V., Verhoeven, V., Vermeire, E., & Coenen, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060348 · Cited by 122 · see citing works
Bacterial target sites for biocide action.
Maillard, J.-Y. (2002) · PubMed · Cited by 118 · see citing works
In Vitro Generation of Neuraminidase Inhibitor Resistance in A(H5N1) Influenza Viruses
Hurt, A. C., Holien, J. K., & Barr, I. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00334-09 · Cited by 116 · see citing works
Ivanova, P. T., Myers, D. S., Milne, S. B., McClaren, J. L., Thomas, P. G., & Brown, H. A. (2015) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5b00040 · Cited by 116 · see citing works
Interim Estimates of 2021–22 Seasonal Influenza Vaccine Effectiveness — United States, February 2022
Chung, J. R., Kim, S. S., Kondor, R. J. G., Smith, C., Budd, A., Tartof, S. Y., Florea, A., Talbot, H. K., Grijalva, C. G., Wernli, K. J., et al. (2022) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7110a1 · Cited by 113 · see citing works
Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation
Burch, J., Paulden, M., Conti, S., Stock, C., Corbett, M. S., Welton, N. J., Ades, A. E., Sutton, A. J., Cooper, N. J., Elliot, A. J., et al. (2009) · Health Technology Assessment · doi:10.3310/hta13580 · Cited by 110 · see citing works
Prevention and Treatment of Seasonal Influenza
Glezen, W. P. (2008) · New England Journal of Medicine · doi:10.1056/nejmcp0807498 · Cited by 99 · see citing works
Błażejewska, P., Kościński, Ł., Viegas, N., Anhlan, D., Ludwig, S., & Schughart, K. (2011) · Virology · doi:10.1016/j.virol.2010.12.047 · Cited by 98 · see citing works
Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017
Flannery, B. L., Chung, J. R., Thaker, S. N., et al. (2017) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6606a3 · Cited by 95 · see citing works
West, J. V. (2002) · British Medical Bulletin · doi:10.1093/bmb/61.1.215 · Cited by 92 · see citing works
Efficacy of Cetylpyridinium Chloride Used as Oropharyngeal Antiseptic
Pitten, F.-A., & Krämer, A. (2011) · Arzneimittelforschung · doi:10.1055/s-0031-1300084 · Cited by 82 · see citing works
Mukherjee, P. K., Esper, F. P., Buchheit, K., Arters, K., Adkins, I., Ghannoum, M. A., & Salata, R. A. (2017) · BMC Infectious Diseases · doi:10.1186/s12879-016-2177-8 · Cited by 64 · see citing works
Self-citationInfections of the Respiratory System
(2010) · Garland Science eBooks · doi:10.1201/9780203833513-33 · Cited by 57 · see citing works
Evolution of the Influenza A Virus Genome during Development of Oseltamivir ResistanceIn Vitro
Renzette, N., Caffrey, D. R., Zeldovich, K. B., Liu, P., Gallagher, G. R., Aiello, D. A., Porter, A. J., Kurt‐Jones, E. A., Bolon, D. N. A., Poh, Y.-P., et al. (2013) · Journal of Virology · doi:10.1128/jvi.01067-13 · Cited by 51 · see citing works
Possible harms of oseltamivir--a call for urgent action.
Jefferson, T., Jones, M., Doshi, P., & Mar, C. D. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61804-3 · Cited by 36 · see citing works
Neuropsychiatric adverse effects of oseltamivir in the FDA Adverse Event Reporting System, 1999-2012
Hoffman, K. B., Demakas, A., Erdman, C. B., et al. (2013) · BMJ · doi:10.1136/bmj.f4656 · Cited by 35 · see citing works
Recommendations for Prevention and Control of Influenza in Children, 2015–2016
(2015) · PEDIATRICS · doi:10.1542/peds.2015-2920 · Cited by 33 · see citing works
Maillard, J., Hann, A. C., Beggs, T. S., et al. (1995) · Journal of Medical Microbiology · doi:10.1099/00222615-42-6-415 · Cited by 30 · see citing works
Surfactive and antibacterial activity of cetylpyridinium chloride formulations in vitro and in vivo
Busscher, H. J., White, D. J., Atema‐Smit, J., et al. (2008) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2008.01230.x · Cited by 28 · see citing works
Infections of the respiratory system
Bindayna, K. M., & Alsalman, J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95092-3.00006-8 · Cited by 10 · see citing works
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Research works printed but not linked: 4
- Popkin DL, Zilka S, Dimaano M, Fujioka H, Rackley C, Salata R, Griffith A, Mukherjee PK, Ghannoum MA, Esper F Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo. Pathogens and Immunity. 2017; 2(2): 253– 69. doi: 10.20411/pai.v2i2.200 PMC5605151 28936484
- [10]Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM, Centers for Disease C, Prevention. Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60(1): 1– 24. PubMed PMID: 21248682. 21248682
- [21]Lu PJ, Santibanez TA, Williams WW, Zhang J, Ding H, Bryan L, O'Halloran A, Greby SM, Bridges CB, Graitcer SB, Kennedy ED, Lindley MC, Ahluwalia IB, LaVail K, Pabst LJ, Harris L, Vogt T, Town M, Singleton JA Surveillance of influenza vaccination coverage--United States, 2007-08 through 2011-12 influenza seasons. MMWR Surveill Summ. 2013; 62(4): 1– 28. PubMed PMID: 24157710. 24157710
- [33]Press A, editor. Virological Methods: ASM Press; 2009.
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Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection
Bao, L., Zhang, C., Dong, J., Zhao, L., Li, Y., & Sun, J. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01840 · Cited by 207 · see citing works
- Authors
- Popkin, D. L., Zilka, S., Dimaano, M., Fujioka, H., Rackley, C., Salata, R., Griffith, A., Mukherjee, P. K., Ghannoum, M. A., & Esper, F.
- Affiliations
- University Hospitals of Cleveland (US)
- University of Chicago (US)
- Case Western Reserve University (US)
- Corresponding author
- Esper, Frank
- ORCID
- Venue
- Pathogens and Immunity
- Publisher
- Case Western Reserve University
- Published
- 2017-06-26
- Volume
- 2
- Issue
- 2
- Pages
- 253
- ISSN
- 2469-2964 (ISSN-L)
- PMC
- PMC5605151
- OpenAlex
- W2721177488
- Cited by
- 123
- References
- 43
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 16 · 2022: 31 · 2021: 29 · 2020: 20 · 2019: 4 · 2018: 3
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Pathogens and Immunity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs (I01 BX002719)
- American Skin Association
- Case Western Reserve University (AI036219, P30 AI036219)
- National Institutes of Health (AI036219, DK097948)
- Center for AIDS Research, University of Washington (P30 AI036219)
- National Institute of Allergy and Infectious Diseases (P30AI036219)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK097948), P30DK097948)
- National Institute of Dental and Craniofacial Research (R01DE024228)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- cetylpyridinium chloride, influenza virus, virucidal activity, oseltamivir resistance, quaternary ammonium compounds, antiviral agents, antiviral resistance
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