The field of drug discovery has seen significant progress in recent years. These advances drive the development of new technologies for testing compound’s effectiveness, as well as their adverse effects on organs and tissues. As an auxiliary tool for drug discovery, smart biomaterials and biopolymers produced from biodegradable monomers allow the manufacture of multifunctional polymeric devices capable of acting as biosensors, of incorporating bioactives and biomolecules, or even mimicking organs and tissues through self-association and organization between cells and biopolymers. This review discusses in detail the use of natural monomers for the synthesis of hydrogels via green routes. The physical, chemical and morphological characteristics of these polymers are described, in addition to emphasizing polymer–particle–protein interactions and their application in proteomics studies. To highlight the diversity of green synthesis methodologies and the properties of the final hydrogels, applications in the areas of drug delivery, antibody interactions, cancer therapy, imaging and biomarker analysis are also discussed, as well as the use of hydrogels for the discovery of antimicrobial and antiviral peptides with therapeutic potential.

The innate immune protection provided by cationic antimicrobial peptides (CAMPs) has been shown to extend to antiviral activity, with putative mechanisms of action including direct interaction with host cells or pathogen membranes. The lack of therapeutics available for the treatment of viruses such as Venezuelan equine encephalitis virus (VEEV) underscores the urgency of novel strategies for antiviral discovery. American alligator plasma has been shown to exhibit strong in vitro antibacterial activity, and functionalized hydrogel particles have been successfully employed for the identification of specific CAMPs from alligator plasma. Here, a novel bait strategy in which particles were encapsulated in membranes from either healthy or VEEV‐infected cells was implemented to identify peptides preferentially targeting infected cells for subsequent evaluation of antiviral activity. Statistical analysis of peptide identification results was used to select five candidate peptides for testing, of which one exhibited a dose‐dependent inhibition of VEEV and also significantly inhibited infectious titers. Results suggest our bioprospecting strategy provides a versatile platform that may be adapted for antiviral peptide identification from complex biological samples.