Protein Nanoparticles for Targeted SARS-CoV-2 Trapping and Neutralization

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge global health despite widespread vaccination efforts, underscoring the need for innovative strategies to combat emerging infectious diseases effectively. Herein, LCB1-NPs and LCB3-NPs are engineered as a novel class of protein-only nanoparticles formed through coiled coil-driven self-assembly and tailored to interact specifically with the SARS-CoV-2 spike protein. The multivalency of LCB1-NPs and LCB3-NPs offers a strategy for efficiently targeting and neutralizing SARS-CoV-2 both in solution and when immobilized on surfaces. It is demonstrated that LCB1-NPs and LCB3-NPs bind to the SARS-CoV-2 spike protein's receptor-binding domain (RBD) with high affinity, effectively blocking the entry of SARS-CoV-2 virus-like particles into angiotensin-converting enzyme 2 (ACE2)-coated human cells. The cost-effectiveness, scalability, and straightforward production process of these protein nanoparticles make them suitable for developing novel anti-viral materials. Accordingly, it is shown how these nanostructures can be packed into columns to build up economic and highly potent trapping devices for SARS-CoV-2 adsorption. This study presents the development of LCB1/LCB3-NPs, protein-only nanoparticles that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by binding the spike protein with low-nanomolar affinity. These nanoparticles demonstrate efficient viral neutralization and hold potential for applications such as SARS-CoV-2 diagnostics, surface functionalization, or viral-adsorbing devices. As proof-of-concept, they are packed into small columns, showing high virus-retention and neutralization capacity, thus creating effective SARS-CoV-2 filtering devices. image