Screening Peptide Drug Candidates To Neutralize Whole Viral Agents: A Case Study with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


Ozcelik C. E., Araz C. Z., Yilmaz O., Gulyuz S., Ozdamar P., Salmanli E., ...Daha Fazla

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, cilt.7, sa.4, ss.1032-1042, 2024 (ESCI) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7 Sayı: 4
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1021/acsptsci.3c00317
  • Dergi Adı: ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus
  • Sayfa Sayıları: ss.1032-1042
  • Anahtar Kelimeler: biotechnological drug development, COVID-19, enzyme-linked immunosorbent assay, peptide-based therapeutics, phage display library, SARS-CoV-2
  • Ankara Üniversitesi Adresli: Evet

Özet

The COVID-19 pandemic revealed the need for therapeutic and pharmaceutical molecule development in a short time with different approaches. Although boosting immunological memory by vaccination was the quickest and robust strategy, still medication is required for the immediate treatment of a patient. A popular approach is the mining of new therapeutic molecules. Peptide-based drug candidates are also becoming a popular avenue. To target whole pathogenic viral agents, peptide libraries can be employed. With this motivation, we have used the 12mer M13 phage display library for selecting SARS-CoV-2 targeting peptides as potential neutralizing molecules to prevent viral infections. Panning was applied with four iterative cycles to select SARS-CoV-2 targeting phage particles displaying 12-amino acid-long peptides. Randomly selected peptide sequences were synthesized by a solid-state peptide synthesis method. Later, selected peptides were analyzed by the quartz crystal microbalance method to characterize their molecular interaction with SARS-CoV-2's S protein. Finally, the neutralization activity of the selected peptides was probed with an in-house enzyme-linked immunosorbent assay. The results showed that scpep3, scpep8, and scpep10 peptides have both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule. The results of this study have a translational potential with future in vivo and human studies.