Department of Ophthalmology and Visual Sciences, University of Illinois Medical Center, Chicago, IL 60612, USA.
Department of Ophthalmology and Visual Sciences, University of Illinois Medical Center, Chicago, IL 60612, USA; Department of Bioengineering, University of Illinois, Chicago, IL 60607, USA.
Antiviral Res. 2020 Aug;180:104814. doi: 10.1016/j.antiviral.2020.104814. Epub 2020 May 5.
Herpes simplex virus-1 (HSV-1) infection is known to cause skin blisters, keratitis as well as deadly cases of encephalitis in some situations. Only a few therapeutic modalities are available for this globally prevalent infection. Very recently, a small molecule BX795 was identified as an inhibitor of HSV-1 protein synthesis in an ocular model of infection. In order to demonstrate its broader antiviral benefits, this study was aimed at evaluating the antiviral efficacy, mode-of-action, and toxicity of BX795 against HSV-1 infection of three human cell lines: HeLa, HEK, and HCE. Several different assays, including cell survival analysis, imaging, plaque analysis, Immunoblotting, and qRT-PCR, were performed. In all cases, BX795 demonstrated low toxicity at therapeutic concentration and showed strong antiviral benefits. Quite interestingly, cell line-dependent differences in the mechanism of antiviral action and cytokine response to infection were seen upon BX795 treatment. Taken together, our results suggest that BX795 may exert its antiviral benefits via cell-line specific mechanisms.
单纯疱疹病毒-1（HSV-1）感染已知会导致皮肤水疱、角膜炎，在某些情况下还会导致致命的脑炎。对于这种在全球普遍存在的感染，只有少数治疗方法可用。就在最近，一种小分子 BX795 在眼部感染模型中被鉴定为 HSV-1 蛋白合成的抑制剂。为了证明其更广泛的抗病毒益处，本研究旨在评估 BX795 对三种人类细胞系（HeLa、HEK 和 HCE）HSV-1 感染的抗病毒功效、作用模式和毒性。进行了几种不同的测定，包括细胞存活分析、成像、蚀斑分析、免疫印迹和 qRT-PCR。在所有情况下，BX795 在治疗浓度下表现出低毒性，并显示出强大的抗病毒益处。有趣的是，在用 BX795 处理后，观察到抗病毒作用机制和细胞因子对感染的反应存在细胞系依赖性差异。总之，我们的结果表明，BX795 可能通过细胞系特异性机制发挥其抗病毒益处。
