Ionic Contra-Viral Therapy (ICVT); a new approach to the treatment of DNA virus infections.
The sequestration of cellular K(+) has been shown elsewhere to elicit a broad spectrum of antiviral activity. The obligatory, coupled cotransports of Na(+), K(+) and Cl(-) (NKCC1) and of Na(+) and K(+) (NKATPase) effect net cellular K(+) influx. We examined the effects of specific inhibitors of these transports; a cardiac glycoside (Digoxin) and a loop diuretic (Furosemide) on virus replication in vitro. The replication of the DNA viruses, herpes simplex virus, varicella zoster virus, human cytomegalovirus and adenovirus was inhibited. There was normal replication of the RNA virus encephalomyocarditis virus. Antiviral activities of both drugs were influenced by extracellular K(+). Antiviral effects were most potent when Digoxin and Furosemide were used in combination. Targeting the host cell in this way is fundamentally different to other antiviral drug developments to date and we propose the descriptive term Ionic Contra Viral Therapy (ICVT) for the purpose of definition. We believe that specific inhibitors of coupled K(+) transports merit controlled clinical trial for a broad spectrum of DNA virus infections by local application.
Hartley
C
C
Henderson Morley Plc, Moseley, Birmingham, UK. ch@henderson-morley.com
Hartley
M
M
Pardoe
I
I
Knight
A
A
D000998:Antiviral Agents / Q000627:therapeutic use*; D004266:DNA Virus Infections / Q000188:drug therapy*; D004267:DNA Viruses / Q000187:drug effects / Q000302:isolation & purification; D004077:Digoxin / Q000627:therapeutic use*; D005665:Furosemide / Q000627:therapeutic use*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D004077:Digoxin; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase