Feron Benedita K L, Gomez Timothy, Youens Natalie C, Mahmoud Nourhan A M, Abdelrahman Hadeer K S, Bugert Joachim J, Richardson Simon C W
Exogenix Laboratory, School of Science, University of Greenwich, Central Avenue, Chatham, Kent, ME4 4TB, UK.
Department of Biochemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451, Egypt.
Virus Genes. 2025 Jun;61(3):342-354. doi: 10.1007/s11262-025-02152-4. Epub 2025 Mar 30.
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 Huh-7 cells from ZIKV cytopathic effects was recorded after electroporation and the siRNA Feron-Zv2, resulting in 122.7 ± 5.3% cell viability (n = 3 ± standard error of the mean (SEM), 100 nM siRNA) after exposure to ZIKV relative to a virus treated control (35.2 ± 7.1% cell viability (n = 3 ± SEM)). Protection of BHK-21 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, 25 nM 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, 75 nM 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.
治疗病毒感染需要有治愈性药物。小干扰（si）RNA提供了这样一种前景，但需要开发安全、有效且非嗜肝性的亚细胞递送系统。在此，对5种靶向寨卡病毒（ZIKV）基因组内特定序列的候选siRNA分子进行了检测，以评估它们在体外降低ZIKV诱导的细胞病变效应的能力。在电穿孔后记录了Huh-7细胞免受ZIKV细胞病变效应的情况，以及siRNA Feron-Zv2的作用，相对于病毒处理的对照（细胞活力为35.2±7.1%（n = 3±平均标准误差（SEM））），在暴露于ZIKV后，Feron-Zv2导致细胞活力达到122.7±5.3%（n = 3±SEM，100 nM siRNA）。在用含有RNA结合结构域的减毒炭疽毒素转染后，记录了BHK-21细胞的保护情况。用Feron-Zv4处理后，在暴露于ZIKV后细胞活力为75.1±2.9%（n = 3±SEM，25 nM siRNA）。这种保护作用在一个含有八聚体PA的系统中得到了体现，在用Feron-Zv2处理后，报告的最大细胞活力为86.2±4.4%（n = 3±SEM，75 nM siRNA）。乱序siRNA没有提供可测量的保护作用。在此，我们首次报告，由减毒炭疽毒素或形成八聚体的ATx递送的siRNA可以保护哺乳动物细胞免受ZIKV细胞病变效应的影响。
