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Consecutive alternating administration as an effective anti-coxsackievirus B3 in vivo treatment scheme

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Abstract

Although chemotherapy is generally indicated for treatment of enterovirus infections, antivirals are currently not used in clinical practice. The use of monotherapy is the main reason for this unfavourable state. This is related to the fact that enterovirus progeny consist of innumerable quasispecies, allowing the virus to develop drug resistance quickly. Here, we present a consecutive alternating administration (CAA) treatment scheme for combining enterovirus inhibitors. Applying the CAA approach with a combination of pleconaril (capsid binder), guanidine HCl (viral 2C inhibitor), and oxoglaucine (PI4KB inhibitor) (PGO) was found to be effective in the treatment of newborn mice infected with a massive inoculum (20 MLD50) of the coxsackievirus B3 cardiotropic Woodruff or neurotropic Nancy strain. In addition to preventing drug resistance, the CAA approach resulted in the parallel development of increased susceptibility to the compounds in the PGO combination. These observations demonstrate the therapeutic potential of the CAA approach for treatment of enterovirus infections.

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Funding

This study was funded by the Bulgarian Academy of Sciences according to the National Program “Young Scientists” (grant number DFNP-56).

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Authors and Affiliations

  1. Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Academician Georgi Bonchev Street, 1113, Sofia, Bulgaria

    Adelina Stoyanova & Angel S. Galabov

Authors
  1. Adelina Stoyanova
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  2. Angel S. Galabov
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Correspondence to Angel S. Galabov.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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This article does not contain any studies with human participants performed by any of the authors. All applicable institutional and/or national guidelines for the care and use of animals were followed. Animal breeding and experiments were conducted in accordance with the guidelines of Bulgaria’s Directorate of Health Prevention and Humane Behaviour towards Animals and European Communities Council Directives 86/609/ EEC.

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Stoyanova, A., Galabov, A.S. Consecutive alternating administration as an effective anti-coxsackievirus B3 in vivo treatment scheme. Arch Virol 166, 1869–1875 (2021). https://doi.org/10.1007/s00705-021-05057-3

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  • DOI: https://doi.org/10.1007/s00705-021-05057-3

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