OligoBinders: Bioengineered Soluble Amyloid-like Nanoparticles to Bind and Neutralize SARS-CoV-2

Molood Behbahanipour, Roger Benoit, Susanna Navarro*, Salvador Ventura*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a primary health concern. Molecules that prevent viral entry into host cells by interfering with the interaction between SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 receptor (ACE2r) opened a promising avenue for virus neutralization. Here, we aimed to create a novel kind of nanoparticle that can neutralize SARS-CoV-2. To this purpose, we exploited a modular self-assembly strategy to engineer OligoBinders, soluble oligomeric nanoparticles decorated with two miniproteins previously described to bind to the S protein receptor binding domain (RBD) with high affinity. The multivalent nanostructures compete with the RBD-ACE2r interaction and neutralize SARS-CoV-2 virus-like particles (SC2-VLPs) with IC50 values in the pM range, preventing SC2-VLPs fusion with the membrane of ACE2r-expressing cells. Moreover, OligoBinders are biocompatible and significantly stable in plasma. Overall, we describe a novel protein-based nanotechnology that might find application in SARS-CoV-2 therapeutics and diagnostics.

Original languageEnglish
Pages (from-to)11444-11457
Number of pages14
JournalACS Applied Materials and Interfaces
Issue number9
Publication statusPublished - 8 Mar 2023


  • antiviral agents
  • coronavirus
  • nanoparticles
  • protein assemblies
  • SARS-CoV-2
  • soluble oligomers
  • spike protein
  • virus inactivation


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