Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus

Abstract

Covid19 pandemic revealed the reality for the need of therapeutic and pharmaceutical molecule development in a short time with different approaches. Although the enhancement of immunological memory by vaccination was the quicker and robust strategy, still medication is required for immediate treatment for a patient. For this purpose, one of the approaches is developing new therapeutic molecule development like peptide-based drugs. Also, peptides can be used developing other molecules like nanobodies. Here, M13 phage display library was used for selecting SARS-CoV-2 interacting peptides for developing a neutralizing molecule for further use. Biopanning was applied with four iterative cycles to select phages displaying different 12-amino acid-long peptides. Then, the M13 phage genomic region where peptide sequences expressed were analyzed and sequences were obtained. Randomly selected peptide sequences were synthesized by solid-state peptide synthesis method. These peptides were analyzed by quartz crystal microbalance method in terms or peptide interaction capacity with specifically wild-type S protein. Next, QCM data was further validated by enzyme-linked immunosorbent assay (ELISA) in order to check peptides according to their neutralizing capacity rather than binding to S1 protein. The results showed that, phage display served an opportunity for selecting peptides which can be used and developed further as pharmaceutical molecules. More specifically, scpep3, scpep8 and scpep10 had both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule.