The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom.
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, United Kingdom.
Sci Rep. 2018 Nov 16;8(1):16956. doi: 10.1038/s41598-018-34732-w.
The re-emergence of poxviral zoonotic infections and the threat of bioterrorism emphasise the demand for effective antipoxvirus therapies. Here, we show that carbenoxolone, a pharmacological inhibitor of gap junction function and a compound widely used in cell culture, is capable of hindering the replication of Vaccinia virus, the prototypical poxvirus, in a gap junction-independent manner in a human keratinocyte cell line. Viral protein synthesis occurs in the presence of carbenoxolone but infectious virion formation is minimal, indicating that carbenoxolone blocks viral morphogenesis. Initial viability tests suggested that carbenoxolone was not toxic to cells. However, electron microscopic analysis of carbenoxolone treated cells revealed that it alters the cellular endomembrane system. This widespread ultrastructural damage prevents Vaccinia virus virion assembly. These results strengthen the need for thorough characterisation of the effects of antiviral compounds on the cellular ultrastructure.
痘病毒人畜共患病的再次出现和生物恐怖主义的威胁强调了对有效抗痘病毒疗法的需求。在这里，我们表明，甘草次酸是缝隙连接功能的药理学抑制剂，也是一种在细胞培养中广泛使用的化合物，能够以缝隙连接非依赖性方式在人角质形成细胞系中抑制痘病毒（典型的痘病毒）的复制。病毒蛋白合成在存在甘草次酸的情况下发生，但感染性病毒粒子的形成最小，表明甘草次酸阻断病毒形态发生。初始生存能力测试表明，甘草次酸对细胞没有毒性。然而，对甘草次酸处理的细胞的电子显微镜分析表明，它改变了细胞的内膜系统。这种广泛的超微结构损伤阻止了痘病毒病毒粒子的组装。这些结果加强了对细胞超微结构抗病毒化合物作用进行彻底表征的必要性。
