Feron, Benedita K. L., Gomez, Timothy, Youens, Natalie C., Mahmoud, Nourhan A. M., Abdelrahman, Hadeer K. S., Bugert, Joachim J. and Richardson, Simon C. W. ORCID: https://orcid.org/0000-0002-7927-0649 (2024) Antiviral siRNA delivered using attenuated, Anthrax Toxin Protects Cells from the cytopathic effects of Zika virus. Virus Genes. ISSN 0920-8569 (Print), 1572-994X (Online) (In Press)

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Abstract

Curative drugs are needed for the treatment of viral infections. Small interfering (si)RNA offer such a prospect but require the development of safe, effective and non-hepatotropic subcellular delivery systems. Here, 5 candidate siRNA molecules targeting defined sequences within the Zika virus (ZIKV) genome were assayed for their ability to reduce ZIKV induced cytopathic effects in vitro. The protection of Huh7 cells from ZIKV cytopathic effects was recorded after electroporation and the siRNA Feron-Zv2, resulted in 122.7 ± 5.3% cell viability (n = 3 ± standard error of the mean (SEM), 100nM siRNA) after exposure to ZIKV relative to a virus treated control (35.2 ± 7.1% cell viability (n = 3 ± SEM)). Protection of BHK cells was recorded after transfection with an attenuated anthrax toxin containing an RNA binding domain. Treatment with Feron-Zv4, resulted in 75.1 ± 2.9% cell viability (n = 3 ± SEM, 25nM siRNA) after exposure to ZIKV. This protection was mirrored by a system containing octameric PA where a maximum of 86.2 ± 4.4% cell viability was reported (n = 3 ± SEM, 75nM siRNA)) after treatment with Feron-Zv2. Scrambled siRNA afforded no measurable protection. Here we report for the first time that siRNA delivered by either attenuated anthrax toxin or octamer forming ATx can protect mammalian cells from ZIKV cytopathic effects.

Item Type:	Article
Additional Information:	A Research Square preprint of the paper has been already published online with a CC_BY license and a DOI. This version has not been peer reviewed by a journal. https://doi.org/10.21203/rs.3.rs-5409774/v1 - MP This work is licensed under a CC BY 4.0 License
Uncontrolled Keywords:	Zika, Anthrax Toxin, siRNA, anti-viral, cytosolic delivery
Subjects:	Q Science > Q Science (General) Q Science > QR Microbiology Q Science > QR Microbiology > QR355 Virology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	21 Mar 2025 12:30
URI:	http://gala.gre.ac.uk/id/eprint/50097

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