title: Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model.
abstract: Human rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically.
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Aeri
authors.initials: A
authors.lastname: Shim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jae-Hyoung
authors.initials: JH
authors.lastname: Song
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Bo-Eun
authors.initials: BE
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jeong-Jun
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Inje University, Gimhae, South Korea.
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, South Korea.
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.affiliation: College of Pharmacy, Ajou University, Suwon, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Younggil
authors.initials: Y
authors.lastname: Cha
authors.affiliation: University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.affiliation: University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.affiliation: Chungcheongnam-do Institute of Health and Environmental Research, Daejeon, South Korea.
authors.forename: Kwi Sung
authors.initials: KS
authors.lastname: Park
authors.affiliation: Incurable Diseases Therapeutics Research Center, Korea Research Institute of Bioscience &Biotechnology, Cheongju, South Korea.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
authors.affiliation: Incurable Diseases Therapeutics Research Center, Korea Research Institute of Bioscience &Biotechnology, Cheongju, South Korea.
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017964:Itraconazole / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000821:virology; D008807:Mice, Inbred BALB C; D010850:Picornaviridae Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D012229:Rhinovirus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D017964:Itraconazole; D002784:Cholesterol