Sulphated Cyclodextrins are Potent anti-HIV Agents Acting Synergistically with 2′,3′-dideoxynucleoside Analogues

Abstract

Sulphated cyclodextrins proved to be potent inhibitors of human immunodeficiency virus (HIV), cytomegalovirus (CMV) and herpes simplex virus (HSV) but not other enveloped viruses (i.e. Sindbis virus, respiratory syncytial virus, Tacaribe virus, vesicular stomatitis virus or vaccinia virus). Their mechanism of action against HIV can be attributed to an inhibition of the binding of HIV-1 virions to the cells, as demonstrated by flow cytometric analysis. The sulphated cyclodextrins enhanced the anti-HIV-1 activity of pyrimidine 2′,3′-dideoxyribosides (i.e. azidothymidine, dideoxycytidine, didehydro-dideoxythymidine, fluorodide-oxychlorouridine), in a subsynergistic manner, and the anti-HIV-1 activity of purine 2′,3′-dideoxyribosides (dideoxyadenosine, dideoxyinosine, 2,6-diaminopurine dideoxyriboside) and 9-(2-phosphonylmethoxyethyl)adenine in a synergistic manner. Following intravenous administration of the sulphated cyclodextrins to rabbits, drug serum concentrations were obtained that were 100- to 1000-fold above the minimum inhibitory concentration for HIV or CMV.