INHIBITORY AND LETHAL CONCENTRATIONS OF 9-BETA-D-ARABINOFURANOSYLADENINE AND ITS HYPOXANTHINE-DERIVATIVE VERSUS HERPES-SIMPLEX VIRUS, TYPE-1

  • 1 January 1977
    • journal article
    • research article
    • Vol. 89  (4) , 687-691
Abstract
Minimum inhibitory concentrations [MIC] of 9-.beta.-D-arabinofuranosyladenine (ara-A, adenine arabinoside, vidarabine) and a purified preparation of 9-.beta.-D-arabinofuranosylhypoxanthine (arabinosylhypoxanthine, ara-Hx) at end points of 50% (MIC50) and 100% (MIC100) reduction to challenges of .apprx. 50 pfu [plaque forming units] of herpes simplex virus type 1 (HSV-1) were determined in [green monkey] Vero renal tissue cultures. Adenosine deaminase is universally present in tissue cultures and serum. These same tests were repeated in the presence of a potent inhibitor of adenosine deaminase, R-3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo-4,5-d)-(1,3)-diazepin-8-ol (co-vidarabine, co-ara-A). Addition of co-ara-A to assays of MIC50 or MIC100 for ara-A ensures standard reproducible results which can be compared in different laboratories. After incubations of HSV-1 in infected cultures for 96 h, 35.degree. C with concentrations of ara-A or ara-Hx at .gtoreq. MIC100, cells were scraped and sonicated. Supernates were then reinoculated into Vero flasks free of antiviral agents to determine minimum lethal concentrations (MIC). Standard values (.mu.g/ml) for ara-A with co-ara-A are 11.3 (MIC500), 17.0 (MIC100) and 34.0 (MIC) but are 68.1 (MIC50), 170.4 (MIC100) and 375 (MIC) for ara-Hx. As a virustatic agent (MIC100), ara-A is 10 times more active than ara-Hx. Ara-A and ara-Hx have virucidal potentials which require approximately twice the respective MIC100.

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