Nature Communications (Feb 2024)

Antiviral fibrils of self-assembled peptides with tunable compositions

  • Joseph Dodd-o,
  • Abhishek Roy,
  • Zain Siddiqui,
  • Roya Jafari,
  • Francesco Coppola,
  • Santhamani Ramasamy,
  • Afsal Kolloli,
  • Dilip Kumar,
  • Soni Kaundal,
  • Boyang Zhao,
  • Ranjeet Kumar,
  • Alicia S. Robang,
  • Jeffrey Li,
  • Abdul-Rahman Azizogli,
  • Varun Pai,
  • Amanda Acevedo-Jake,
  • Corey Heffernan,
  • Alexandra Lucas,
  • Andrew C. McShan,
  • Anant K. Paravastu,
  • B. V. Venkataram Prasad,
  • Selvakumar Subbian,
  • Petr Král,
  • Vivek Kumar

DOI
https://doi.org/10.1038/s41467-024-45193-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract 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.