Medicinal chemistry insights into antiviral peptidomimetics

• Published in: Drug discovery today Vol. 28; no. 3; p. 103468
• Main Authors: Ding, Dang, Xu, Shujing, da Silva-Júnior, Edeildo Ferreira, Liu, Xinyong, Zhan, Peng
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2023
• Subjects: antiviral; Antiviral Agents; Chemistry, Pharmaceutical; drug discovery; peptide; Peptides - chemistry; peptidomimetic; Peptidomimetics; strategy; peptide; peptidomimetic; drug discovery; strategy; antiviral
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2022.103468

[Display omitted] •Peptidomimetics are an important class of compounds with improved binding affinities, enhanced metabolic stability, and favorable bioavailability.•Extensive medicinal chemistry strategies for optimizing antiviral peptidomimetics are presented.•Peptidomimetics, as exemplified by Paxlovid, N-0385, and 11L, have been identified as antiviral drugs or drug candidates.•Integrated medicinal chemistry methodologies will be used in designing antiviral peptidomimetics. The (re)emergence of multidrug-resistant viruses and the emergence of new viruses highlight the urgent and ongoing need for new antiviral agents. The use of peptidomimetics as therapeutic drugs has often been associated with advantages, such as enhanced binding affinity, improved metabolic stability, and good bioavailability profiles. The development of novel antivirals is currently driven by strategies of converting peptides into peptidomimetic derivatives. In this review, we outline different structural modification design strategies for developing novel peptidomimetics as antivirals, involving N- or C-cap terminal structure modifications, pseudopeptides, amino acid modifications, inverse-peptides, cyclization, and molecular hybridization. We also present successful recent examples of peptidomimetic designs.