Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat

• Main Authors: Vitor H. Pomin (Author), Fakhri Mahdi (Author), Weihua Jin (Author), Fuming Zhang (Author), Robert J. Linhardt (Author), Jason J. Paris (Author)
• Format: Book
• Published: MDPI AG, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph14080714; 1424-8247
• Keywords: glycoprotein 120; HIV; neuroprotection; surface plasmon resonance; sulfated glycan; trans-activating transcriptor; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 14, Iss 8, p 714 (2021)

The potential neuroprotective capacity of four different sulfated glycans: <i>Botryocladia occidentalis</i>-derived sulfated galactan (BoSG) (MW > 100 kDa), <i>Lytechinus variegatus</i>-derived sulfated fucan (LvSF) (MW~90 kDa), high-molecular weight dextran sulfate (DxS) (MW 100 kDa), and unfractionated heparin (UFH) (MW~15 kDa), was assessed in response to the HIV-1 proteins, R5-tropic glycoprotein 120 (gp120) and/or trans-activator of transcription (Tat), using primary murine neurons co-cultured with mixed glia. Compared to control-treated cells in which HIV-1 proteins alone or combined were neurotoxic, BoSG was, among the four tested sulfated glycans, the only one capable of showing significant concentration-dependent neuroprotection against Tat and/or gp120, alone or combined. Surface plasmon resonance-based data indicate that BoSG can bind both HIV-1 proteins at nM concentrations with preference for Tat (7.5 × 10⁻⁸ M) over gp120 (3.2 × 10⁻⁷ M) as compared to UFH, which bound gp120 (8.7 × 10⁻⁷ M) over Tat (5.7 × 10⁻⁶ M). Overall, these data support the notion that sulfated glycan extracted from the red alga <i>B. occidentalis</i>, BoSG, can exert neuroprotection against HIV-1 Tat and gp120, potentially via direct molecular interactions.