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

• Published in: The Journal of infectious diseases 1980-05, Vol.141 (5), p.563-574
• Main Authors: De Clercq, E., Descamps, J., Verhelst, G., Walker, R. T., Jones, A. S., Torrence, P. F., Shugar, D.
• Format: Article
• Language: English
• Subjects: Antiviral Agents; Antivirals; Cell culture techniques; Cytarabine - therapeutic use; Dosage; Herpes Simplex - drug therapy; Herpesviridae; Human herpesvirus 1; Human herpesvirus 2; Kidney cells; Mutation; Simplexvirus; Simplexvirus - drug effects; Thymidine Kinase - pharmacology; Tilorone - therapeutic use; Vaccinia virus; Vaccinia virus - drug effects; Viral Infections and Antiviral Theraphy; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/141.5.563

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.