Exploiting Peptide Self-Assembly for the Development of Minimalistic Viral Mimetics

Abstract

Viruses are natural supramolecular nanostructures that form spontaneously by molecular self-assembly of complex biomolecules. Peptide self-assembly is a versatile tool that allows mimicking viruses by creating their simplified versions through the design of functional, supramolecular materials with modularity, tunability, and responsiveness to chemical and physical stimuli. The main challenge in the design and fabrication of peptide materials is related to the precise control between the peptide sequence and its resulting supramolecular morphology. We provide an overview of existing sequence patterns employed for the development of spherical and fibrillar peptide assemblies that can act as viral mimetics, offering the opportunity to tackle the challenges of viral infections.

Catalytic Peptides: the Challenge between Simplicity and Functionality

“…Peptide self-assembly is based on the interplay of noncovalent interactions that allow for the formation of various supramolecular higher-order assemblies driven by subtle changes in hydrophobicity, charge, and size of the peptides. [50] These ordered assemblies can be considered mimetics of protein's tridimensional structure rigidity and therefore offer the possibility to incorporate catalytic units into self-assembling molecules and develop efficient catalytic peptides, becoming one of the most successful strategies for the development of minimal catalysts. [12,51] Here, we will summarize self-assembly strategies used in aqueous solutions and their respective advantages (Table 2).…”

Self-Assembling Peptides: From Design to Biomedical Applications

“…Apart for antifouling activities, SAP assemblies can be employed to design viral mimetics as they can act both as structural components and as functional domains that promote cell entry, selective binding, or a specific activity such as catalytic or antimicrobial activities [ 101 ]. SAP-based viral mimetic designs can be divided into two categories.…”

“…For example, capsid morphology has been reconstructed from nanospheres self-assembled from β-annulus peptide segments of Tomato bushy stunt virus and Sesbania mosaic virus [ 102 ]. The second category includes simplified virus-like complexes in which functional peptide units are conjugated with RNA or DNA fragments [ 101 ]. Cao et al designed I3V3A3G3K3 peptide to induce DNA condensation into virus-mimicking structures.…”

Factors influencing the catalytic activity of metal-dependent histidine-rich peptides: sequence, conformation, stereochemistry, self-assembly or their interplay?

“…15,19 Peptide self-assembly is the spontaneous organization of peptides into well-defined structures that display unique physical and chemical properties, different from those of their individual constituent monomers. 22,23 By organizing peptides into specific architectures, it is possible to create catalytic sites with enhanced activity and selectivity. 20,21,24 In addition, peptides are susceptible to proteolytic degradation, have reduced stability in plasma, and limited oral bioavailability.…”