Antiviral targets of a chromene derivative from Sargassum micracanthum in the replication of human cytomegalovirus.
A chromene derivative (1) obtained from a brown alga, Sargassum micracanthum, has been proved to be a potent inhibitor of human cytomegalovirus (HCMV). In the present study, we evaluated its mode of action by various experimental assays. Time-of-addition experiments revealed that 1 was active if applied to cells before viral DNA synthesis, indicating that it inhibited early events of virus replication including virus adsorption and penetration, and a step immediately after viral internalization. Virus attachment and penetration studies suggested that one of the targets for anti-HCMV action of 1 was virus adsorption to cells and to a lesser extent, virus internalization was delayed in the presence of the compound. Pretreatment of virus particles with 1 showed that the compound exerted dose-dependent virucidal action. The chromene derivative and ganciclovir (GCV), an anti-HCMV drug, were synergistic inhibitors when used in combination. The synergistic effect could be explained by inhibition of different steps in HCMV replication cycle produced by 1 and GCV.
Hayashi
Kyoko
K
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyoma, Japan. hayashi9@pha.u-toyoma.ac.jp
Mori
Jun
J
Saito
Haruo
H
Hayashi
Toshimitsu
T
D000998:Antiviral Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D044647:Sargassum / Q000737:chemistry*; D014771:Virion / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D001578:Benzopyrans; D015774:Ganciclovir