SELECTIVE-INHIBITION OF HUMAN CYTOMEGALOVIRUS REPLICATION BY NAPHTHALENEDISULFONIC ACID-DERIVATIVES

Several naphthalenedisulfonic acid derivatives were found to be selective inhibitors of human cytomegalovirus (CMV) replication in MRC-5 cells. Among the test compounds, the bis-naphthalenedisulfonic acid derivative having an hexamethylene spacer emerged as the most potent inhibitor of CMV replication. Its 50% antivirally effective concentration (EC50) for AD-169 strain was 12 muM, whereas the compound did not affect the growth of mock-infected MRC-5 cells at concentrations up to 500 muM. The naphthalenedisulfonic acid derivatives were also inhibitory to CMV clinical isolates. Virus yield reduction assay revealed that the compounds significantly reduced virus growth in CMV-infected MRC-5 cells. The bis-naphthalenedisulfonic acid derivatives with an hexamethylene spacer suppressed the expression of CMV-induced immediate early, and early antigens at a concentration of 20 muM, whereas the anti-CMV nucleoside ganciclovir did not do so even at the concentration that was 10-fold higher than its EC50 for CMV-induced plaque formation. Furthermore, naphthalenedisulfonic acid derivatives had to be present at the time of virus infection to exert their anti-CMV activity. These results suggest that the compounds are targeted at an early event in the virus replicative cycle, presumably, virus adsorption.