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A significant number of antiviral agents used in clinical practice are amino acids, short peptides, or peptidomimetics. Among them, several HIV protease inhibitors (e. g. lopinavir, atazanavir), HCV protease inhibitors (e. g. grazoprevir, glecaprevir), and HCV NS5A protein inhibitors have contributed to a significant decrease in mortality from AIDS and hepatitis. However, there is an ongoing need for the discovery of new antiviral agents and the development of existing drugs; amino acids, both proteinogenic and non‐proteinogenic in nature, serve as convenient building blocks for this purpose. The synthesis of non‐proteinogenic amino acid components of antiviral agents could be challenging due to the need for enantiomerically or diastereomerically pure products. Herein, we present a concise review of antiviral agents whose structures are based on amino acids of both natural and unnatural origin. Special attention is paid to the synthetic aspects of non‐proteinogenic amino acid components of those agents.

Structures of several dozen of known antibacterial, antifungal or antiprotozoal agents are based on the amino acid scaffold. In most of them, the amino acid skeleton is of a crucial importance for their antimicrobial activity, since very often they are structural analogs of amino acid intermediates of different microbial biosynthetic pathways. Particularly, some aminophosphonate or aminoboronate analogs of protein amino acids are effective enzyme inhibitors, as structural mimics of tetrahedral transition state intermediates. Synthesis of amino acid antimicrobials is a particular challenge, especially in terms of the need for enantioselective methods, including the asymmetric synthesis. All these issues are addressed in this review, summing up the current state‐of‐the‐art and presenting perspectives fur further progress.

Antifungal polyene macrolide antibiotics Amphotericin B (AmB) and Nystatin (NYS) were conjugated through the ω-amino acid linkers with diwalled "molecular umbrellas" composed of spermidine-linked deoxycholic or cholic acids. The presence of "umbrella" substituents modulated biological properties of the antibiotics, especially their selective toxicity. Some of the AmB-umbrella conjugates demonstrated antifungal in vitro activity comparable to that of the mother antibiotic but diminished mammalian toxicity, especially the hemolytic activity. In contrast, antifungal in vitro activity of NYS-umbrella conjugates was strongly reduced and all these conjugates demonstrated poorer than NYS selective toxicity. No correlation between the aggregation state and hemolytic activity of the novel conjugates was found.