Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct;8(5):318-324.
doi: 10.24171/j.phrp.2017.8.5.05. Epub 2017 Oct 31.

Antiviral Activity of Itraconazole against Echovirus 30 Infection In Vitro

Jae-Sug Lee  1 , Hwa-Jung Choi  1 , Jae-Hyoung Song  2 , Hyun-Jeong Ko  2 , Kyungah Yoon  3 , Jeong-Min Seong  4
Affiliations

Antiviral Activity of Itraconazole against Echovirus 30 Infection In Vitro

Jae-Sug Lee et al. Osong Public Health Res Perspect. 2017 Oct.

Abstract

Objectives: Echovirus 30 is a major cause of meningitis in children and adults. The aim of this study was to investigate whether the antifungal drug itraconazole could exhibit antiviral activity against echovirus 30.

Methods: The cytopathic effect and viral RNA levels were assessed in RD cells as indicators of viral replication. The effects of itraconazole were compared to those of two known antiviral drugs, rupintrivir and pleconaril. The time course and time-of-addition assays were used to approximate the time at which itraconazole exerts its activity in the viral cycle.

Results: Itraconazole and rupintrivir demonstrated the greatest potency against echovirus 30, demonstrating concentration-dependent activity, whereas pleconaril showed no antiviral activity. Itraconazole did not directly inactivate echovirus 30 particles or impede viral uptake into RD cells, but did affect the initial stages of echovirus 30 infection through interference with viral replication.

Conclusion: Itraconazole can be considered a lead candidate for the development of antiviral drugs against echovirus 30 that may be used during the early stages of echovirus 30 replication.

Keywords: itraconazole; meningitis; viruses.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1
Itraconazole exerts antiviral activity against echovirus 30 in vitro. (A) The antiviral activity and (B) cytotoxicity of itraconazole were evaluated based on the cell viability of RD cells. The cell viability was evaluated by using the sulforhodamine assay and the results were determined based on the absorbance at 562 nm. The bar graphs show the mean ± standard deviation. Ctrl, control; Veh, vehicle.
Figure 2
Figure 2
The time course of echovirus 30 infection. RD cells infected with the 50% cell culture infective dose of echovirus 30 were harvested at the indicated time points after 2 μM itraconazole, 2 μM rupintrivir, or 10 μM pleconaril had been added (i.e., post-infection). The total RNA was isolated and echovirus 30 RNA was analyzed by RT-qPCR.
Figure 3
Figure 3
Time-of-addition experiment testing the effect of itraconazole on the echovirus 30 viral cycle. Itraconazole (2 μM), rupintrivir (2 μM), or pleconaril (10 μM) were added prior to, at the time of, or after viral infection of RD cells, specifically at the indicated time points. The percentage of viable cells was analyzed 14 hours post-infection. RD cells that were treated with drugs prior to viral infection were washed before infection.
Figure 4
Figure 4
Effects of itraconazole on infectivity of echovirus 30 particles. Echovirus 30 particles were incubated with of 2 μM itraconazole, 2 μM rupintrivir, or 10 μM pleconaril for 1 hour at 4°C. RD cells were then incubated in the presence or absence of virus for 1 hour at 37°C. The unbound virus was removed by extensive washing and the incubation was continued with or without 2 μM itraconazole, 2 μM rupintrivir, or 10 μM pleconaril at 37°C. The antiviral activity was determined by RT-qPCR analysis 2 days after infection. −1 h, pre-incubation of virus with the indicated drug without subsequent drug treatment of the infected cells; 0 h, incubation of cells with the indicated drug after viral infection; Ctrl, control; Veh, vehicle.
See this image and copyright information in PMC

References

    1. Rudolph H, Prieto Dernbach R, Walka M, et al. Comparison of clinical and laboratory characteristics during two major paediatric meningitis outbreaks of echovirus 30 and other non-polio enteroviruses in Germany in 2008 and 2013. Eur J Clin Microbiol Infect Dis. 2017 doi: 10.1007/s10096-017-2979-7. In press. https://doi.org/10.1007/s10096-017-2979-7. - DOI - PubMed
    1. Rudolph H, Schroten H, Tenenbaum T. Enterovirus infections of the central nervous system in children: an update. Pediatr Infect Dis J. 2016;35:567–9. doi: 10.1097/INF.0000000000001090. https://doi.org/10.1097/INF.0000000000001090. - DOI - PubMed
    1. Wieczorek M, Krzysztoszek A, Figas A. Molecular characterization of echovirus 30 isolates from Poland, 1995–2015. Virus Genes. 2016;52:400–4. doi: 10.1007/s11262-016-1310-5. https://doi.org/10.1007/s11262-016-1310-5. - DOI - PubMed
    1. Oberste MS, Maher K, Kennett ML, et al. Molecular epidemiology and genetic diversity of echovirus type 30 (E30): genotypes correlate with temporal dynamics of E30 isolation. J Clin Microbiol. 1999;37:3928–33. - PMC - PubMed
    1. Österback R, Kalliokoski T, Lähdesmäki T, et al. Echovirus 30 meningitis epidemic followed by an outbreak-specific RT-qPCR. J Clin Virol. 2015;69:7–11. doi: 10.1016/j.jcv.2015.05.012. https://doi.org/10.1016/j.jcv.2015.05.012. - DOI - PubMed