Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of HIV-1 replication in vitro.
OBJECTIVE
To determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1 in vitro.


METHODS
A sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides.


METHODS
Activity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was measured by a p24 antigen capture enzyme-linked immunosorbent assay.


RESULTS
DS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152.


CONCLUSIONS
DS-4152 has the potential, from these in vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.
Baba
M
M
Department of Microbiology, Fukushima Medical College, Japan.
Shigeta
S
S
Ikeuchi
T
T
Korenaga
H
H
Osada
Y
Y
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016049:Didanosine / Q000494:pharmacology; D015726:Giant Cells / Q000187:drug effects / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D016047:Zalcitabine / Q000494:pharmacology
D000998:Antiviral Agents; D011135:Polysaccharides, Bacterial; C079061:tecogalan; D016047:Zalcitabine; D016049:Didanosine