Popkin Daniel L, Zilka Sarah, Dimaano Matthew, Fujioka Hisashi, Rackley Cristina, Salata Robert, Griffith Alexis, Mukherjee Pranab K, Ghannoum Mahmoud A, Esper Frank
Department of Dermatology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
Center for Medical Mycology, Department of Dermatology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
Pathog Immun. 2017;2(2):252-269. doi: 10.20411/pai.v2i2.200. Epub 2017 Jun 26.
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.
Here, we evaluate the ability of CPC to disrupt influenza viruses and .
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.
The virucidal effect of CPC occurred within 10 minutes, with mean EC and EC 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.
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 .
持续需要预防流感的策略。虽然十六烷基氯化吡啶（CPC）是一种广谱抗菌剂，具有广泛的抗菌谱，但其对呼吸道病毒的影响尚未得到详细研究。
在此，我们评估CPC破坏流感病毒的能力。
评估了CPC对流感病毒敏感株和对奥司他韦耐药株的杀病毒活性。使用血凝试验和组织培养感染剂量试验确定CPC的有效杀病毒浓度（EC）。使用透射电子显微镜（TEM）评估CPC对病毒包膜形态和超微结构的影响。在亚抑制浓度的CPC中多次传代后，评估流感病毒产生耐药性的能力。最后，使用PR8小鼠流感模型评估CPC制剂预防和治疗流感感染的疗效。
对于大多数测试的流感毒株，无论其类型和对奥司他韦的耐药性如何，CPC的杀病毒作用在10分钟内发生，平均EC和EC范围在5至20μg/mL之间。使用TEM检查表明，CPC破坏了病毒包膜的完整性及其形态。尽管长时间暴露，流感病毒对CPC未表现出耐药性。与未治疗的小鼠相比，治疗的小鼠存活率显著提高且体重维持稳定。
抗菌剂CPC通过靶向和破坏病毒包膜对流感病毒的敏感株和耐药株具有杀病毒活性。即使在非常低的CPC浓度下也能看到显著的杀病毒活性，且不会产生耐药性。此外，CPC制剂可降低流感相关的死亡率和发病率。
