Phage Display of Combinatorial Peptide Libraries: Application to Antiviral Research

Abstract

Given the growing number of diseases caused by emerging or endemic viruses, original strategies are urgently required: (1) for the identification of new drugs active against new viruses and (2) to deal with viral mutants in which resistance to existing antiviral molecules has been selected. In this context, antiviral peptides constitute a promising area for disease prevention and treatment. The identification and development of these inhibitory peptides require the high-throughput screening of combinatorial libraries. Phage-display is a powerful technique for selecting unique molecules with selective affinity for a specific target from highly diverse combinatorial libraries. In the last 15 years, the use of this technique for antiviral purposes and for the isolation of candidate inhibitory peptides in drug discovery has been explored. We present here a review of the use of phage display in antiviral research and drug discovery, with a discussion of optimized strategies combining the strong screening potential of this technique with complementary rational approaches for identification of the best target. By combining such approaches, it should be possible to maximize the selection of molecules with strong antiviral potential.

Peptide P3 Selected from Phage Display Screen Shows Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus

“…In the +4 h group, P3 was added at 4 h after virus infection, and we calculated that P3 entered the cells probably at 5-6 h. In this 5-6 h period, viruses had enough time to complete intracellular capsid removal and polymerase expression [29,[33][34][35]. Based on these results, we suggest that P3 plays an inhibitory role, and its inhibition efficiency was comparatively much lower than that of the -4 h group and 0 h group.…”

A 45-Amino-Acid Scaffold Mined from the PDB for High-Affinity Ligand Engineering

“…Knottins often use grafting of known binding motifs, which is only applicable to a subset of targets (Ackerman et al, 2014), although binders have been evolved from naïve libraries (Getz et al, 2011). Peptides, partially due to limited potential for interfacial area as well as the entropic cost of conformational flexibility (Castel et al, 2011), often require extensive optimization to yield the affinity and specificity required for many applications. In addition, the multiple disulfide bonds required for stabilization can complicate production and range of application in both cases.…”

The D-form of a novel heparan binding peptide decreases cytomegalovirus infection in vivo and in vitro

“…Peptides offer several benefits as therapeutics. They can be readily synthesized, designed to be highly specific, easily modified to enhance biological activity, and less toxic because they are catabolized into amino acids (Castel et al, 2011). However, their susceptibility to proteases and short serum half-life have historically limited the use of peptides as therapeutics (McGregor, 2008).…”