Assessing the Impact of Agents with Antiviral Activities on Transmembrane Ionic Currents: Exploring Possible Unintended Actions

Geng-Bai Lin, Chia-Lung Shih, R. Liutkeviciene, V. Rovite, E. So, Chaochao Wu, Sheng Nan Wu
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Abstract

As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such as cell membrane ion channels in diverse cell types. In this review paper, we demonstrate that many different drugs or compounds, in addition to their known interference with viral infections, may also directly influence various types of ionic currents on the surface membrane of the host cell. These agents include artemisinin, cannabidiol, memantine, mitoxantrone, molnupiravir, remdesivir, SM-102, and sorafenib. If achievable at low concentrations, these regulatory effects on ion channels are highly likely to synergize with the identified initial mechanisms of viral replication interference. Additionally, the immediate regulatory impact of these agents on the ion-channel function may potentially result in unintended adverse effects, including changes in cardiac electrical activity and the prolongation of the QTc interval. Therefore, it is essential for patients receiving these related agents to exercise additional caution to prevent unnecessary complications.
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评估具有抗病毒活性的制剂对跨膜离子电流的影响:探索可能的意外作用
随着有效抗病毒治疗需求的增加,如冠状病毒疾病 19(COVID-19)感染,了解这些药物或化合物的作用机制似乎显而易见,但它们也可能与未探索的靶点(如不同类型细胞中的细胞膜离子通道)发生相互作用,这一点至关重要。在这篇综述论文中,我们证明了许多不同的药物或化合物除了已知的干扰病毒感染外,还可能直接影响宿主细胞表面膜上的各种离子电流。这些药物包括青蒿素、大麻二酚、美金刚、米托蒽醌、莫诺吡拉韦、雷米替韦、SM-102 和索拉非尼。如果可以在低浓度下实现,这些对离子通道的调节作用极有可能与已确定的病毒复制干扰初始机制产生协同效应。此外,这些药物对离子通道功能的直接调节作用可能会导致意想不到的不良反应,包括心电活动改变和 QTc 间期延长。因此,接受这些相关药物治疗的患者必须格外谨慎,以防止出现不必要的并发症。
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