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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection relies on its spike protein binding to angiotensin-convertingenzyme 2 (ACE2) on host cells to initiate cellular entry. Blockingthe interactions between the spike protein and ACE2 offers promisingtherapeutic opportunities to prevent infection. We report here onpeptide amphiphile supramolecular nanofibers that display a sequencefrom ACE2 in order to promote interactions with the SARS-CoV-2 spikereceptor binding domain. We demonstrate that displaying this sequenceon the surface of supramolecular assemblies preserves its alpha-helicalconformation and blocks the entry of a pseudovirus and its two variantsinto human host cells. We also found that the chemical stability ofthe bioactive structures was enhanced in the supramolecular environmentrelative to the unassembled peptide molecules. These findings revealunique advantages of supramolecular peptide therapies to prevent viralinfections and more broadly for other targets as well.

Automated summary

This study reports a method that blocks the interaction between SARS-CoV-2 and ACE2 by displaying ACE2 sequence on the surface of supramolecular nanofibers, offering promising therapeutic opportunities to prevent viral infection. The results demonstrate that this method maintains the secondary structure of ACE2 and blocks the entry of pseudovirus and its variants into human cells, while enhancing the chemical stability of bioactive structures in the supramolecular environment. These findings reveal the unique advantages of supramolecular peptide therapies for preventing viral infections and other targets.