Antiviral fibrils of self-assembled peptides with tunable compositions

Nature Communications volume  15, Article number: 1142 (2024 ) Cite this article

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized β-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.

In recent decades, many novel viruses originating in the animal kingdom have been spreading in the rapidly growing human population. Among them, the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, has claimed millions of lives worldwide and overwhelmed global healthcare systems for several years1. During the infection process, the viral ‘Spike’ protein binds the angiotensin-converting enzyme 2 (ACE2) receptor that is expressed ubiquitously in human cells2,3,4. The mRNA vaccines developed against SARS-CoV-2 have proven to be an effective strategy against severe disease and death in infected patients, and whilst more effective against early viral strains; their protection against new viral variants becomes less efficient, unless they are based on new viral strains5.

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