Amlodipine and Diltiazem Significantly Repress Human Rotavirus Infection In Vitro.

Pegah Khales, Hossein Keyvani, Angila Ataei-Pirkooh, Mohammad Mehdi Saghafi, Farah Bokharaei-Salim, Saied Ghorbani, Seyed Hamidreza Monavari, Seyed Jalal Kiani, Maryam Esghaei, Mohammad Farahmand, Shirin Sayyahfar, Khadijeh Khanalih, Zahra Habib, Ahmad Tavakoli
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引用次数: 0

Abstract

Background: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication.

Objective: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection.

Methods: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID50, and real-time PCR assays.

Results: The highest inhibitory effect was obtained at concentrations of 0.5 μg/ml of amlodipine and 3 μg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the Ct values compared to the virus control, respectively (p-value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 μg/ml of amlodipine and above 25 μg/ml of diltiazem.

Conclusion: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection.

氨氯地平和地尔硫卓对体外轮状病毒感染的抑制作用
背景:考虑到钙在轮状病毒复制和形态发生中的作用,假设使用钙通道阻滞剂降低细胞质钙水平可随后干扰轮状病毒复制。目的:研究氨氯地平和地尔硫卓两种钙离子通道阻滞剂对人轮状病毒感染的作用。方法:采用中性红法观察药物对MA-104细胞的细胞毒作用。采用细胞病变效应抑制、TCID50和实时PCR检测无毒浓度的氨氯地平和地尔硫卓对人轮状病毒的影响。结果:氨氯地平浓度为0.5 μg/ml、地尔硫卓浓度为3 μg/ml时,与病毒对照相比,传染性轮状病毒滴度分别降低4.6倍和5.5倍,Ct值分别增加4倍和5倍(p值< 0.001)。相反,当氨氯地平浓度高于0.9 μg/ml和地尔硫卓浓度高于25 μg/ml时,传染性轮状病毒滴度与病毒对照组相比显著升高。结论:本研究提示除了心血管疾病外,最佳剂量的钙通道阻滞剂也可用于治疗轮状病毒感染引起的胃肠炎。
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