{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T04:44:33Z","timestamp":1766551473609,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Effective therapy against the influenza virus is still an unmet goal. Drugs with antiviral effects exist, but the appearance of resistant viruses pushes towards the discovery of drugs with different mechanisms of action. New anti-influenza molecules should target a good candidate, as a new anti-influenza molecule could be an inhibitor of the influenza A virus hemagglutinin (HA), which plays a key role during the early phases of infection. In previous work, we identified two tetrapeptide sequences, SLDC (1) and SKHS (2), derived from bovine lactoferrin (bLf) C-lobe fragment 418\u2013429, which were able to bind HA and inhibit cell infection at picomolar concentration. Considering the above, the aim of this study was to synthesize a new library of peptidomimetics active against the influenza virus. In order to test their ability to bind HA, we carried out a preliminary screening using biophysical assays such as surface plasmon resonance (SPR) and orthogonal immobilization-free microscale thermophoresis (MST). Biological and computational studies on the most interesting compounds were carried out. The methods applied allowed for the identification of a N-methyl peptide, S(N-Me)LDC, which, through high affinity binding of influenza virus hemagglutinin, was able to inhibit virus-induced hemagglutination and cell infection at picomolar concentration. This small sequence, with high activity, represents a good starting point for the design of new peptidomimetics and small molecules.<\/jats:p>","DOI":"10.3390\/ijms241814268","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T23:11:52Z","timestamp":1695165112000},"page":"14268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rational Design of Novel Peptidomimetics against Influenza A Virus: Biological and Computational Studies"],"prefix":"10.3390","volume":"24","author":[{"given":"Maria Carmina","family":"Scala","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-4976","authenticated-orcid":false,"given":"Magda","family":"Marchetti","sequence":"additional","affiliation":[{"name":"National Centre for Innovative Technologies in Public Health, National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-7598","authenticated-orcid":false,"given":"Fabiana","family":"Superti","sequence":"additional","affiliation":[{"name":"National Centre for Innovative Technologies in Public Health, National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy"},{"name":"Association for Research on Integrative Oncology Therapies (ARTOI) Foundation, Via Ludovico Micara, 73, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-0051","authenticated-orcid":false,"given":"Mariangela","family":"Agamennone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-2181","authenticated-orcid":false,"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-7215","authenticated-orcid":false,"given":"Marina","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.cell.2009.01.029","article-title":"The influenza virus enigma","volume":"136","author":"Salomon","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ITC33","DOI":"10.7326\/AITC201709050","article-title":"Influenza","volume":"167","author":"Uyeki","year":"2017","journal-title":"Ann. 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