Inhibitory effect of (S)-HPMPC, (S)-HPMPA, and 2'-nor-cyclic GMP on clinical ocular adenoviral isolates is serotype-dependent in vitro.
Currently, there is no effective treatment for ocular adenoviral infections that occur in epidemics worldwide, produce significant patient morbidity, and cause substantial economic losses. We tested several new antivirals in vitro, and found that (S)-HPMPC, (S)-HPMPA, and 2'-nor-cyclic GMP demonstrated significant serotype-dependent inhibitory activity by plaque reduction assay (ID50 = 0.017-17.0 micrograms/ml) against common clinical ocular isolates and standard adenoviral serotypes (Ad 1, Ad 5, Ad 8, and Ad 19). (S)-HPMPC was the least toxic (CD50 in A549 cells = 306 micrograms/ml), and (S)-HPMPC and (S)-HPMPA had high selectivity indices.
Gordon
Y J
YJ
Eye and Ear Institute of Pittsburgh, PA 15213.
Romanowski
E
E
Araullo-Cruz
T
T
Seaberg
L
L
Erzurum
S
S
Tolman
R
R
De Clercq
E
E
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000258:Adenovirus Infections, Human / Q000382:microbiology; D000260:Adenoviruses, Human / Q000145:classification / Q000187:drug effects*; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003236:Conjunctivitis, Viral / Q000382:microbiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012703:Serotyping; D014407:Tumor Cells, Cultured; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D006147:Guanine; C045511:9-((2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl)guanine P-oxide; D003596:Cytosine; D004247:DNA; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000077404:Cidofovir