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.
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.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Bernaerts
R
R
Verbruggen
A
A
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents; D002499:Centrifugation, Density Gradient; D003517:Cyclopentanes / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D018139:Simplexvirus / Q000187:drug effects / Q000378:metabolism; D014709:Vero Cells
D000998:Antiviral Agents; D003517:Cyclopentanes; D004279:DNA, Viral; C030360:5-(2-iodovinyl)-2'-deoxyuridine; C045201:1-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-(2-iodovinyl)-2,4-(1H,3H)-pyrimidinedione; D007065:Idoxuridine; D003857:Deoxyuridine