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Pathog Immun. 2017;2(2):252-269. doi: 10.20411/pai.v2i2.200. Epub 2017 Jun 26.

Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo.

Author information

1
Department of Dermatology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
2
Center for Medical Mycology, Department of Dermatology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
3
Department of Medicine, The University of Chicago, Chicago, Illinois.
4
Electron Microscopy Core Facility, Case Western Reserve University School of Medicine.
5
Hathaway Brown Science Research and Engineering Program, Cleveland, Ohio.
6
Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
7
Division of Pediatric Infectious Diseases, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.

Abstract

BACKGROUND:

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:

CPC; Cetylpyridinium Chloride; Influenza; Respiratory tract illness; quaternary ammonium compound; respiratory virus

Conflict of interest statement

TRANSPARENCY DECLARATIONS MAG acts as Chief Scientific Officer and Consultant for ARMS Pharmaceutical LLC. PKM acts as a Consultant for ARMS Pharmaceutical LLC. There is no conflict of interest for the remaining authors regarding the publication of this paper.

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