Amlodipine and Diltiazem Significantly Repress Human Rotavirus Infection In Vitro

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