web analytics

Hydrocarbon-Stapled Peptides To Inhibit SARS-CoV-2 Viral Infection

Interests: Infectious Disease
Published:
Lead Inventor: James LaBelle
Print or Save to PDF

SUMMARY

  • The SARS-CoV-2 virus spreads by binding its spike protein to the human angiotensin-converting enzyme 2 (hACE2) protein expressed at the cell surface of lungs, arteries, heart, kidney, and intestines.
  • The inventors have developed 12 hydrocarbon stapled peptides that bind to the viral spike protein.  Delivered by nanoparticles, these peptides mimic the human ACE2 receptor, which SARS-CoV-2’s spike protein binds to in order to enter the host cell.
  • Their single and double-stapled hydrocarbon peptides maintain their secondary shape at a wide range of biologically relevant temperatures. They inhibit binding and entry of the SARS-CoV-2 virus through molecular mimicry. 
  • The inventors aim to further develop hydrocarbon-stapled peptides as intravenous and nebulized nanocarriers for COVID-19 drugs. 

FIGURE

A) Structural interaction between the SARS-CoV-2’s spike protein Receptor Binding Domain (RBD) and the 𝛼1 helix of the ACE2 protein.  B) Protein-Protein Interaction (PPI) of SARS-CoV-2-ACE2 stapled hydrocarbons.  RBD residues are shown in red and highlighted in the stapled alpha helical peptides (SAHPs) of the 𝛼1 helix. Hydrocarbon-stapled RBD residues at positions i, (i+4) are shown in blue.

ADVANTAGES

ADVANTAGES

  • Addresses protein-protein interaction (PPI) between RBD and hACE2 to directly inhibit SARS-CoV-2 viral infection.
  • Superior bioavailability, proteolytic resistance, and target cell delivery compared to current COVID-19 therapeutic options.
  • Hydrocarbon-staple packaging based on previous breakthroughs with peptide amphiphile (PA) and polymersome nanoparticles. 

APPLICATIONS

  • SARS-CoV-2