# Insights into the self-assembly and interaction of sars-cov-2 fusion peptides with biomimetic plasma membranes

## TL;DR

This study explores how SARS-CoV-2 fusion peptides interact with cell membranes, revealing how they help the virus enter cells and suggesting new ways to design antiviral materials.

## Contribution

The study reveals a loaded-spring mechanism for membrane remodeling by SARS-CoV-2 fusion peptides, offering new insights into viral entry and nanomaterial design.

## Key findings

- FPs form supramolecular assemblies that exclude cholesterol-rich nanodomains and increase membrane fluidity.
- Spiral FP fibers support a loaded-spring mechanism for cooperative membrane remodeling.
- The findings highlight potential applications in antiviral strategies and nanobiotechnology.

## Abstract

First identified in late 2019, the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, rapidly escalated into a global health crisis. SARS-CoV-2 is a single-stranded RNA virus encased in a lipid envelope that houses key structural proteins, including the Spike glycoprotein, which mediates viral entry into host cells. Within Spike, the S2 subunit, and particularly its fusion domain, plays a critical role in merging viral and host membranes. To explore how receptor-driven Spike clustering influences this process, we investigated the self-assembly of S2 fusion peptides (FPs) and their interactions with biomimetic plasma membrane (PM) models composed of phospholipids, sphingomyelin, and cholesterol. Atomic force microscopy, laser direct infrared spectroscopy, neutron reflectometry, and grazing-incidence X-ray diffraction reveal that FPs form supramolecular assemblies that exclude cholesterol-rich nanodomains, increase membrane fluidity, and disrupt raft-like order associated with ACE2 binding. The appearance of spiral FP fibers supports a loaded-spring mechanism for membrane remodeling, offering a model for cooperative peptide-driven fusion, highlighting opportunities for antiviral and nanobiotechnological applications.

This study shows how SARS-CoV-2 fusion peptides assemble and reshape membranes, revealing cooperative mechanisms that lower barriers to viral entry and offering principles for designing antiviral and membrane-responsive nanomaterials.