Inhibitory effect of dibenzofuran and dibenzosuberol derivatives on rhinovirus replication in vitro; effective prevention of viral entry by dibenzosuberenone
Ma. Murray et Lm. Babe, Inhibitory effect of dibenzofuran and dibenzosuberol derivatives on rhinovirus replication in vitro; effective prevention of viral entry by dibenzosuberenone, ANTIVIR RES, 44(2), 1999, pp. 123-131
A series of derivatives of dibenzofuran and dibenzosuberol block rhinovirus
replication in vitro as judged by their ability to hinder the cytopathic e
ffect in cells infected with HRV14 or HRV16. Both the number and the size o
f viral plaques were reduced effectively by treatment with these compounds
in a dose-dependent fashion, thus affecting viral spread. The compound 2-hy
droxy-3-dibenzofuran carboxylic acid was equally effective against HRV16 an
d HRV14, with IC50 values of 25 mu M in cytopathy assays. Dibenzosuberenone
showed minor differences in selectivity, with IC50 values of 10 and 30 mu
M for HRV16 and HRV14 cytopathy, respectively. Likewise, dibenzosuberenone
effectively prevented the production of HRV16 proteins, viral RNA, and infe
ctious virus particles when present at concentrations above 30 mu M. Time-o
f-addition experiments show that compounds must be administered before or d
uring the viral adsorption step in order to be effective antivirals. Dibenz
osuberenone can block the adsorption of viral particles on to cells, preven
ting further steps in the replication cycle, but is not effective as a dire
ct inactivating agent. These compounds likely interact with viral capsid pr
oteins, affecting receptor interactions required for attachment and subsequ
ent entry into cells. (C) 1999 Elsevier Science B.V. All rights reserved.