Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model

Shim, Aeri; Song, Jeho; Kwon, Bo Eun; Lee, Su Hwan; Ahn, Jae‐Jun; Kim, Yeon Jeong; Rhee, Ki Jong; Chang, Suk-Joon; Cha, Younggil; Lee, Yong Soo; Kweon, Mi Na; Park, Kwi Sung; Kim, Dong-Eun; Cho, Sungchan; Cho, Hyun‐Jong; Ko, Hyun‐Jeong

doi:10.1038/srep23110

Cited by 32 publications

(38 citation statements)

References 42 publications

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“…Unfortunately, PI4KB inhibition was found to be associated with adverse side effects 91,92 . OSBP inhibitors include the antifungal drug itraconazole (Sporanox) 93 , which was shown to have antiviral activity in mice 94 .…”

Section: Heterogeneous Nuclear Ribonucleoprotein Cmentioning

confidence: 99%

The life cycle of non-polio enteroviruses and how to target it

et al. 2018

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The genus Enterovirus (EV) of the family Picornaviridae includes poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These diverse viruses cause a variety of diseases, including non-specific febrile illness, hand-foot-and-mouth disease, neonatal sepsis-like disease, encephalitis, paralysis and respiratory diseases. In recent years, several non-polio enteroviruses (NPEVs) have emerged as serious public health concerns. These include EV-A71, which has caused epidemics of hand-foot-and-mouth disease in Southeast Asia, and EV-D68, which recently caused a large outbreak of severe lower respiratory tract disease in North America. Infections with these viruses are associated with severe neurological complications. For decades, most research has focused on poliovirus, but in recent years, our knowledge of NPEVs has increased considerably. In this Review, we summarize recent insights from enterovirus research with a special emphasis on NPEVs. We discuss virion structures, host-receptor interactions, viral uncoating and the recent discovery of a universal enterovirus host factor that is involved in viral genome release. Moreover, we briefly explain the mechanisms of viral genome replication, virion assembly and virion release, and describe potential targets for antiviral therapy. We reflect on how these recent discoveries may help the development of antiviral therapies and vaccines.

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Section: Heterogeneous Nuclear Ribonucleoprotein Cmentioning

confidence: 99%

The life cycle of non-polio enteroviruses and how to target it

et al. 2018

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“…Other OSBP inhibitors (e.g., 25-hydroxycholesterol, AN-12-H5, T-00127-HEV2, TTP-8307, and the natural compound OSW-1) also impaired enterovirus replication [56,[63][64][65]. In a rhinovirus mouse model, prophylactic intranasal treatment with itraconazole reduced viral titers and pathology, raising expectations for topically applied itraconazole to prevent or treat common colds [66].…”

Section: Pi4kbmentioning

confidence: 99%

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Bauer

Lyoo

Schaar

et al. 2017

Current Opinion in Virology

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Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.

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“…Recently, three novel epidithiodiketopiperazines (KCN-2,2’-epi-19, KCN-19 and KCN-21) were synthesized that displayed activity against RV-87 [ 33 ]. Interestingly, the antifungal compound itraconozole has recently been found to have in vitro and in vivo antiviral activity in RV infection [ 61 ]. This was potentially due to inhibition of cellular cholesterol trafficking, a process the authors suggest, in accord with another study [ 62 ], is essential for RV replication.…”

Section: Introductionmentioning

confidence: 99%

“…For example, both oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III β (PI4KB), have been identified as host proteins involved in picornavirus replication [ 133 , 134 , 135 ], and studies focusing upon chemical inhibition of PI4KB with a panel of aminothiazoles have demonstrated potent inhibition of RV [ 136 ]. Equally, novel enviroxime-like compounds as well as other compounds such as itraconozole (mentioned above) which can target OSBP have also shown promise in inhibiting viral replication [ 61 , 62 , 134 , 137 ]. Furthermore, as both PI4KB and OSBP can act as substrates for protein kinase D (PKD), recent studies have identified PKD as a key molecule in RV replication and have demonstrated that PKD inhibition can profoundly affect RV replication at an early stage [ 138 ].…”

Section: Introductionmentioning

confidence: 99%

Antiviral Therapeutic Approaches for Human Rhinovirus Infections

et al. 2018

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Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immunosuppressed and exacerbations of pre-existing pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Many of these conditions can place significant economic costs upon healthcare infrastructure. There is currently no licensed vaccine for rhinovirus, as the large variety of rhinovirus serotypes has posed significant challenges for research. In this review, we discuss current knowledge around antiviral drugs and small molecule inhibitors of rhinovirus infection, as well as antiviral host defense peptides as exciting prospects to approach the development of novel therapeutics which target human rhinovirus.

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Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model

Cited by 32 publications

References 42 publications

The life cycle of non-polio enteroviruses and how to target it

The life cycle of non-polio enteroviruses and how to target it

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Antiviral Therapeutic Approaches for Human Rhinovirus Infections

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