Supramolecular Nanofibers Block SARS-CoV-2 Entry into Human Host Cells

Area of Science:

• Biochemistry
• Materials Science
• Virology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike protein to bind angiotensin-converting enzyme 2 (ACE2) on host cells for entry.
• Inhibiting spike protein-ACE2 interactions presents a viable therapeutic strategy against viral infections.

Purpose of the Study:

• To develop supramolecular nanofibers displaying an ACE2-derived sequence to block SARS-CoV-2 spike protein binding.
• To evaluate the efficacy of these nanofibers in preventing viral entry and assess their stability.

Main Methods:

• Design and synthesis of peptide amphiphile supramolecular nanofibers displaying an ACE2 sequence.
• Assessment of the α-helical conformation of the displayed ACE2 sequence within the supramolecular assembly.
• Testing the inhibition of pseudovirus (including variants) entry into human host cells.

Main Results:

• The supramolecular nanofibers successfully displayed the ACE2 sequence, maintaining its α-helical structure.
• These nanofibers effectively blocked the entry of SARS-CoV-2 pseudoviruses and their variants into host cells.
• The supramolecular environment enhanced the chemical stability of the bioactive peptide structures.

Conclusions:

• Supramolecular peptide therapies utilizing ACE2-mimicking nanofibers are effective in preventing SARS-CoV-2 cellular entry.
• The enhanced stability and efficacy highlight the potential of supramolecular assemblies for antiviral applications.
• This approach offers a promising platform for developing new therapies against viral infections and other diseases.