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

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.

Highly Potent Peptide Therapeutics To Prevent Protein Aggregation in Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disorder resulting from a significant amplification of CAG repeats in exon 1 of the Huntingtin (Htt) gene. More than 36 CAG repeats result in the formation of a mutant Htt (mHtt) protein. These amino-terminal mHtt fragments lead to the formation of misfolded proteins, which then form aggregates in the relevant brain regions. Therapies that can delay the progression of the disease are imperative to halting the course of the disease. Peptide-based drug therapies provide such a platform. Inhibitory peptides were screened against monomeric units of both wild type (Htt(Q25)) and mHtt fragments, Htt(Q46) and Htt(Q103). Fibril kinetics was studied by utilizing the Thioflavin T (ThT) assay. Atomic force microscopy was also used to study the influence of the peptides on fibril formation. These experiments demonstrate that the chosen peptides suppress the formation of fibrils in mHtt proteins and can provide a therapeutic lead for further optimization and development.