title: 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-beta-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-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)-uracil (BVaraU), vidarabine (9-beta-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 micrograms/ml to 0.9 micrograms/ml. Then followed BTDU and CTDU (IC50 1-2 micrograms/ml), the sulfated polysaccharides (IC50 1.3-5.8 micrograms/ml), the phosphonylmethoxyalkyl derivatives (IC50 5.6-25 micrograms/ml),ara-A (IC50 11 micrograms/ml) and PFA (IC50 38.5 micrograms/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).
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: P
authors.initials: P
authors.lastname: Goubau
authors.forename: J
authors.initials: J
authors.lastname: Desmyter
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006367:HeLa Cells; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C057479:oxetanocin G; C091173:9-(3-hydroxy-2-phosphonomethoxypropyl)-2,6-diaminopurine; D006147:Guanine; D003596:Cytosine; D006493:Heparin; D016264:Dextran Sulfate; D000225:Adenine; D000077404:Cidofovir; D000212:Acyclovir