Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2

Area of Science:

• Biochemistry
• Virology
• Drug Discovery

Background:

• Host cell heparan sulfate proteoglycans (HSPGs) play a crucial role in viral binding and entry.
• Developing inhibitors that mimic HSPGs can block early-stage viral infections.

Purpose of the Study:

• To synthesize and evaluate hexavalent sulfoglycodendrimers (SGDs) as potential inhibitors of HIV-1 and SARS-CoV-2.
• To investigate the interaction mechanisms of SGDs with these viruses at a molecular level.

Main Methods:

• Synthesis of seven hexavalent sulfoglycodendrimer candidates.
• HIV neutralization assay to determine anti-HIV activity.
• Molecular dynamics simulations to analyze SGD-pathogen interactions.

Main Results:

• Sub-micromolar anti-HIV activity was observed for the most effective SGD candidates.
• SGDs bind multivalently to HIV-1 glycoprotein 120 (gp120) and SARS-CoV-2 Receptor Binding Domain (RBD).
• Interactions involve polybasic regions of gp120 and ACE2/HSPG binding sites on the SARS-CoV-2 RBD.

Conclusions:

• Hexavalent sulfoglycodendrimers exhibit significant potential as broad-spectrum antiviral agents.
• SGDs effectively inhibit the early binding and entry stages of HIV-1 and SARS-CoV-2.
• Further development of SGDs could lead to novel therapeutic strategies against viral infections.