Table 1.
Examples of Ca++ effects in viral infection, and their inhibition by CCBs or other calcium blocking or reducing agents
| Virus | Alterations to Ca++ | Comments | Refs. |
|---|---|---|---|
| Porcine coronavirus PDCoV | Infection leads to upregulation of intracellular Ca++ concentrations | Treatment with CCB (diltiazem) inhibited viral replication | 31 |
| Murine coronavirus | Infection induced rapid calcium increase in about 5% of cells (apparently those infected by multiple viruses) | CCB verapimil inhibited viral replication | 39 |
| SARS CoV and MERS | Ca++ required for viral entry | CCBs inhibit SARS CoV infection in vitro | 40 |
| Recovirus | Increased cytosolic Ca++ levels mediated by viroporin NS1-2 shown to facilitate viral replication | Virus yield reduced by experimental Ca++ reduction | 41 |
| Dengue virus | Infected cells show increased permeability to Ca++, mediated by virus | Ca++ increases favored viral replication; virus yield reduced by Ca++ reduction | 42 |
| Hepatitis B virus | HBx protein stimulates Ca++ entry into cells | Reduction of Ca++ impaired viral replication | 43 |
| West Nile virus | Infection leads to rapid Ca++ influx into cells, via calcium channels | Treatment with CCBs (verapamil, diltiazem, nifedipine) decreased viral yield | 28 |
| Dengue, hepatitus C and Zika | Cellular ion channel TRPV4 mediates Ca++ influx | Blocking of TRPV4 channel reduced viral infectivity | 30 |
| Herpes virus | Infection induces rapid and transient increased in intracellular Ca++ | Ca++ alteration mediates viral entry into cells | 44 |
| Phelbovirus | Infectivity mediated by Ca++ influx into cells | CCBs (benidipine or nifedipine) reduced intracellular Ca++ and improved survival in mouse model and in human retrospective study | 45 |
| Influenza A | Infection triggers influx of Ca++ | CCBs (verapimil and diltiazem) inhibit viral infection | 46–48 |
| Rotavirus | Influx of Ca++ early in infection due to viroporin NSP4 | Viroporin-defective mutant lacked Ca++ conductivity | 32, 49 |
| Filoviruses (Ebola and Marburg) | Viral entry into cells requires Ca++ permeable ion channel TPC2 | Calcium channel blocker verapamil (and other channel blockers) inhibit viral cell entry | 50, 51 |
| Coxsackievirus | Influx of Ca++ early in infection due to viroporin 2B | Viroporin with mutations showed low infectivity | 32, 52 |
| Cytomegalovirus | Virus induces early influx of Ca++ from extracellular environment, perhaps via viroporin US21 | CCBs nifedipine, verapamil and manidipine inhibit virus | 53, 54 |