{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:47:51Z","timestamp":1763038071309,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Pistachio Growers (APG), Fresno, CA (USA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Since the onset of the COVID-19 (COronaVIrus Disease 19) pandemic, SARS-CoV-2 has exhibited a high transmission rate, further enhanced by new variants able to better adapt to humans. Addressing this issue has been challenging due to viral resistance and side effects associated with antiviral drugs and vaccines. As a result, there has been a growing interest in plant-derived compounds with antiviral properties. Our study revealed that pistachio extracts significantly inhibited SARS-CoV-2 viral entry. Employing pseudotyped particles bearing the S protein of SARS-CoV-2, we demonstrated that treatment with pistachio extracts inhibited binding of alpha (\u03b1) and omicron (\u03bf) SARS-CoV-2 variants. Furthermore, our study revealed that the pistachio carotenoid zeaxanthin exhibited a different inhibitory activity against two SARS-CoV-2 variants. In silico analyses demonstrated a strong interaction between zeaxanthin and the receptor-binding domain (RBD) domain of the omicron spike (S) protein, thus reducing pseudovirus entry. However, zeaxanthin\u2019s weaker interaction with the alpha variant\u2019s RBD was insufficient to inhibit entry. Additionally, zeaxanthin suppressed the expression of the host protease TMPRSS2 at the protein level, thereby limiting the internalization of the alpha variant, which relies on TMPRSS2 for cellular entry.<\/jats:p>","DOI":"10.3390\/ijms26041667","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:41:47Z","timestamp":1739763707000},"page":"1667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Selective Control by Pistacia vera L. and Its Carotenoid Zeaxanthin on SARS-CoV-2 Virus"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3474-6057","authenticated-orcid":false,"given":"Rosamaria","family":"Pennisi","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cG. Natta\u201d, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Trischitta","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"},{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di sotto 8, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-4069","authenticated-orcid":false,"given":"Davide","family":"Barreca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-2151","authenticated-orcid":false,"given":"Antonio","family":"Rescifina","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, V. le A. Doria, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-3702","authenticated-orcid":false,"given":"Giuseppina","family":"Mandalari","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-7724","authenticated-orcid":false,"given":"Maria Teresa","family":"Sciortino","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1001\/jama.2020.0757","article-title":"Coronavirus Infections\u2014More Than Just the Common Cold","volume":"323","author":"Paules","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus Biology and Replication: Implications for SARS-CoV-2","volume":"19","author":"Kratzel","year":"2021","journal-title":"Nat. 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