Antiviral activity of NMSO3 against adenovirus in vitro.
NMSO3, a sulfated sialyl lipid, was evaluated for its efficacy against adenovirus (AdV) in vitro. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of AdV type 2 (AdV2), type 4 (AdV4), type 8 (AdV8) and type 37 (AdV37) was 0.21-0.71 microg/ml in HEp-2 cells and 1.01-1.41 microg/ml in MKN-28 cells. The EC(50) values of NMSO3 were lower than those of HPMPC and ddC, which were also evaluated. NMSO3 exhibited minimal cytotoxicity against HEp-2 cells and MKN-28 cells, both for which the median cytotoxic concentration (50% cytotoxic concentration, CC(50)) was more than 1000 microg/ml. NMSO3 was the most potent and selective anti-AdV compound of those examined. NMSO3 inhibited AdV infection of HEp-2 cells only when present during the virus adsorption period. A virus binding assay using radiolabeled AdV4 revealed that NMSO3 inhibited viral binding to the HEp-2 cells. NMSO3 itself bound to the virus particles, but not to the HEp-2 cell membrane. Thus, the mechanism of anti-AdV activity by NMSO3 involves inhibition of virus adsorption to cells by NMSO3 binding to viral particles.
Kaneko
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Department of Ophthalmology, Fukushima Medical University School of Medicine, 1, Hikarigaoka, Fukushima 960-1295, Japan. h-kane@chive.ocn.ne.jp
Kato
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Mori
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Shigeta
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D000256:Adenoviridae / Q000187:drug effects* / Q000502:physiology; D000327:Adsorption / Q000187:drug effects; D000998:Antiviral Agents / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
C413863:(2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate; D000998:Antiviral Agents; D008055:Lipids; D019158:N-Acetylneuraminic Acid