Deoxyadenosine but not adenosine reversed the antiviral activity of 9-β-d-arabinofuranosyladenine (ara-A) and 9-β-d-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase.
In suspension cultures of KB cells, 10 µm ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 µm deoxyadenosine reduced the antiviral activity of 10 µm ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 µm by 2 µm deoxyadenosine and to 8.5 µm by 10 µm deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive.
The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 µm to 70, 91, or 121 µm by the concurrent addition of 5, 10, or 20 µm deoxyadenosine. Competitive antagonism could not be demonstrated.
In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available until recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.
Presented in part to the Sixteenth Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Ill., October 27, 1976 (39). Supported by USPHS Grant DE 02731 from the National Institute of Dental Research.