Comparative Efficacy of Antiherpes Drugs against Different Strains of Herpes Simplex Virus

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Abstract
A large variety of antiherpes compounds was compared for their inhibitory activity against laboratory strains and clinical isolates of herpes simplex virus (HSV) type 1 and type 2. From studies performed in primary rabbit kidney cell cultures, six, E-5-(2-bromovinyl)-2′-deoxyuridine, E-5-(2-iodovinyl)-2′-deoxyuridine, 5-vinyl-2′deoxyuridine, 2′-fluoro-5-iodoaracytosine, acycloguanosine, and 5-iodo-2′-deoxycytidine, emerged as the most potent and selective antiherpes agents. For HSV type 1, the 50% inhibitory doses (m so) were 0.008, 0.012, 0.018, 0.017, 0.04, and 0.06 μg/ml, respectively; those for HSV type 2 were 1,2,0.1,0.05,0.04, and 0.3 μg/ml, respectively. These compounds did not inhibit host-cell metabolism or replication of vaccinia virus except at concentrations 100–10,000 times greater than the ID50 for any HSV. All were significantly less inhibitory for a thymidine kinase (TK)-deficient mutant of HSV type 1 than for normal strains, suggesting that phosphorylation by virus-induced TK was required to produce specific inhibition of HSV replication.

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