Abstract：
:The bicyclams represent a new class of highly potent and selective HIV inhibitors. Time-of-addition experiments have previously shown that these compounds interfere with an early event in the viral replicative cycle. Additional experiments have now been carried out in order to investigate in more detail the mechanism of action of these promising compounds. As described in this paper, PCR experiments revealed that no viral DNA was formed following viral infection, thus confining the target(s) of action of the bicyclams to an early stage of HIV infection. An assay, using pseudotype virions containing the envelope of HIV-1 and the genome of a plaque-forming virus (Cocal Virus), pointed to viral entry as the main target of the bicyclams. HIV-1 strains resistant to two prototype bicyclams, JM2763 and SID791 (JM3100), were raised. Results obtained with SID791 with respect to syncytium formation induced by SID791-sensitive and -resistant HIV-1 strains and the cross-resistance observed for dextran sulfate, suggest inhibition of binding and/or fusion as a plausible target of SID791. Additional experiments enabled us to exclude SID791 and JM2763 as binding inhibitors and to conclude that bicyclams block the entry of cell-bound virus. Furthermore, a monoclonal antibody recognising the V3 loop of wild-type gp120 did not bind to this region in the two bicyclam-resistant strains. Our results point to gp120 as a possible target for the HIV-inhibitory effects of the bicyclams.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
De Vreese K,Reymen D,Griffin P,Steinkasserer A,Werner G,Bridger GJ,Esté J,James W,Henson GW,Desmyter J,Anné J,De Clercq Idoi
10.1016/0166-3542(95)00837-3subject
Has Abstractpub_date
1996-03-01 00:00:00pages
209-19issue
2-3eissn
0166-3542issn
1872-9096pii
0166-3542(95)00837-3journal_volume
29pub_type
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