Verapamil inhibits influenza A virus replication

Abstract

Calcium channel blockers reduce Ca++ flux through membrane channels and may inhibit intracellular Ca++-dependent synthetic and regulatory activities by binding to calmodulin. We have found that Verapamil, a calcium channel blocker, inhibits influenza virus replication in Madin-Darby canine kidney cells and in murine pulmonary macrophages and that this antiviral effect occurs with drug addition late in the replication cycle. Chlorpromazine, a drug which binds to calmodulin, also inhibited influenza virus replication in these tissue culture systems. We suggest that Verapamil and chlorpromazine inhibit influenza virus replication by interfering with calmodulin-dependent intracellular activities necessary for late synthetic steps or virus assembly steps and that calcium channel blockers provide a new probe for investigating influenza virus replication.

Inhibition of Growth of Chlamydia trachomatis by the Calcium Antagonist Verapamil

“…Other investigators have also demonstrated an inhibitory effect of Verapamil on replication of human cytomegalovirus (Albrecht et al, 1984), Epstein-Barr virus (Nemerov & Cooper, 1984) and influenza virus (Nugent & Shanley, 1984). Taken together, these results clearly demonstrate that Verapamil exhibits anti-viral and anti-chlamydia1 activity in uitro.…”

Verapamil has Antiviral Activities that Target Different Steps of the Influenza Virus Replication Cycle

“…Beside its calcium channel blocking activity, Verapamil also affects PKC activation [14]. In IV-infected cells, the PKC inhibition impairs ERK-activation [12], which is essential for efficient nuclear RNP export at the late stage (6-10 h p.i.)…”

“…Figure 1A) is long known to reduce influenza virus replication [14]. In order to analyse this antiviral effect in more detail, we first defined the cytotoxic concentration of Verapamil at which 50% of A549 cells (as an example for human alveolar epithelia cells) are still viable (CC 50 ).…”

“…To elucidate whether Verapamil would indeed only be important for late steps in IAV replication as supposed before [14], we performed an entry assay using pseudotyped retroviral particles (PRP) expressing the HA, NA and M2 protein of the influenza virus strain A/Thailand/KAN-1/2004 (KAN-1, H5N1) and carrying the GFP-reporter gene (H5N1-PRP). To determine the entry-inhibition capacity of Verapamil, A549 cells were incubated with a dilution of the H5N1-PRP stock followed by the addition of Verapamil in different concentrations at the indicated time points (0, 0.5, 1, 1.5, 3, 5, and 24 h).…”

“…The inhibitory effects of Verapamil on IAV propagation in cell culture have been described many years ago [14]. Based on the observation that chlorpromazine, a calmoduline-binding drug, also inhibited IAV replication, it was suggested that both drugs may interfere with calmoduline-dependent intra-cellular activities that are required for (late steps) of IAV replication or assembly.…”