Role of the incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine and its carbocyclic analogue into DNA of herpes simplex virus type 1- infected cells in the antiviral effects of these compounds

J Balzarini, R Bernaerts, A Verbruggen and E De Clercq

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

The carbocyclic analogue of (E)-5-(2-iodovinyl)-2'-deoxyuridine (C- IVDU) is, like its parent compound (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), a potent and selective inhibitor of herpes simplex virus type 1 (HSV-1). There is a close correlation between the inhibition of viral DNA synthesis and the antiviral activity of both IVDU and C-IVDU. IVDU and C-IVDU inhibit viral DNA synthesis at 0.2 and 0.5 microM, respectively, and interfere with cellular DNA synthesis at concentrations that are 10- to 40-fold in excess of their antivirally effective doses. At concentrations affording a similar antiviral effect, C-[125I]IVDU is incorporated into viral and cellular DNA of HSV- 1-infected Vero cells to a 7- to 10-fold lesser extent than IVDU. [125I]IVDU but not C-[125I]IVDU leads to breakage of both DNA strands when incorporated into HSV-1 DNA.

Volume 37, Issue 3, pp. 402-407, 03/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics