Inhibitors of the Sodium Potassium ATPase that Impair Herpes Simplex Virus Replication Identified Via a Chemical Screening Approach. Herpes simplex virus (HSV) is a common human pathogen. It attaches to the surface of human cells and enters into the cells. HSV viral DNA is inserted into the nucleus of the cell and the viral genome is copied. Viral products are produced which leave the cell. Much is known and more can be learned about HSV by studying small molecule inhibitors that target these different stages of the virus.
Ouabain is a well-known cardiac glycoside. It is a Na+/K+-ATPase inhibitor and has been reported to be anti-viral. Ouabain has been found to inhibit HSV replication after entry into the cell and before gene expression and without toxicity. Ouabain was found to be one of the most active in a screening of 480 molecules.
Testing doses of ouabain are in the nanomolar (nM) range. Ouabain was found to reduce the viral yield by 100-fold to 10,000-fold. The antiviral effects were not toxic to the cells. The effect of ouabain was reduced if given 8 hours after the infection started. Ouabain did not alter the stages of attachment or entry into cells. Ouabain was found to inhibit the expression of genes.
Bufalin, a cardiac glycoside from toad venom, was more potent against HSV than ouabain.
CONCLUSION: Ouabain was found to inhibit HSV replication without cell toxicity. The Na/K pump is involved. The exact mechanism is not known. Bufalin was another cardiac glycoside found to inhibit HSV. They have not been tested against HSV in humans.
NOTE: Bufalin is one of a few animal origin cardiac glycosides used in Chinese medicine. It is known to be stronger than ouabain. Such agents have effects similar to digitoxin and are used for cardiac therapy. Ginsengs are cardiac glycosides, but, have not been tested against HSV.