Comparative activity of various compounds against clinical strains of herpes simplex virus

Abstract

The following compounds were evaluated for their inhibitory activity against clinical strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in both primary rabbit kidney (PRK) and HeLa cell cultures: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), 9-(2-phosphonylmethoxyethyl)adenine (PMEA), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), (RS)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine (HPMPDAP), 5-(5-bromothien-2-yl)-2′-deoxyuridine (BTDU), 5-(5-chlorothien-2-yl)-2′-deoxyuridine (CTDU), 9-(2-deoxy-2-hydroxymethyl-β-D-erythro-oxetanosyl)guanine (OXT-G), pentosan polysulfate, heparin, dextran sulfate (MW 10,000), acyclovir, 9-(2-hydroxyethoxymethyl)guanine (ACV), (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU), 1-β-D-arabinofuranosyl-(E)-5-(2-bromovinyl)-uracil (BVaraU), vidarabine (9-β-D-arabinofuranosyladenine) (ara-A) and phosphonoformate (PFA). The most potent inhibitors of HSV-1 were (in order of decreasing activity in PRK cells) BVDU, ACV, BVaraU and OXT-G, their mean 50 % inhibitory concentration (IC50) ranging from 0.02 μg/ml to 0.9 μg/ml. Then followed BTDU and CTDU (IC50 1-2 μg/ml), the sulfated polysaccharides (IC50 1.3-5.8 μg/ml), the phosphonylmethoxyalkyl derivatives (IC50 5.6-25 μg/ml), ara-A (IC50 11 μg/ml) and PFA (IC50 38.5 μg/ml). Except for BVDU, BVaraU, BTDU and CTDU, the compounds did not discriminate between HSV-2 and HSV-1. All the compounds studied could be considered specific anti-HSV agents. Their selectivity indexes varied from 3 (PFA) to 6400 (BVDU). © 1992 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH.