Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis

Abstract

The polysulfated polyxylan HOE/BAY946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carries in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (aN) values in the presence of HOE/BAY946 or dextran sulfate 5000. Accordingly, h-1p/h-1H ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2D194 in the presence of HOE/BAY946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus.

Antiviral Activity of Sulfated Polysaccharide of Adenanthera pavonina against Poliovirus in HEp‐2 Cells

“…To substantiate this feature, we analyzed the SPLS Ap effect directly on viral particles (virucidal assay) and its interaction with cell receptors (inhibition of adsorption assay) resulting in low activity. The presence of β -glucans in the SPLS Ap and the possibility of interferon induction cannot be ruled out, as suggested by Biesert et al [36]. We also demonstrated that SPLS Ap showed effect when used after infection.…”

The in vitro antiviral property of Azadirachta indica polysaccharides for poliovirus

“…These compounds could interfere in the synthesis of viral proteins or at viral expression in the regulation of the intracellular or transmembrane signaling pathway (Gonzalez et al, 1987;Biesert et al, 1990). Our results showed that the tested polysaccharides maintained the antiviral effect even when added 1 and 2 h after infection, although with a lower percentage of viral inhibition compared to time 0 h. This also suggests an effect during viral replication, for example, in the synthesis of proteins of PV-1.…”

A New Procedure for the Isolation of Anti-HIV Compounds (Polysaccharides and Polyphenols) from the Marine Alga Fucus vesiculosus

“…Only the compound HOE/BAY 946, a polysulfated polyxylan, may differ in its mode of action from the other sulfated polysaccharides. It acts pleiotropically by increasing the hydrophobicity of the lymphocyte membranes suppressing HIV-protein synthesis and reducing release of HIV particles from the infected peripheral blood mononuclear cells in vitro (39,40). Until further structural and mechanistic studies are performed, we have no explanation for the anti-HIV and for the well established anticoagulant effect of the fucoidan subfractions isolated (41).…”