{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:24:48Z","timestamp":1760149488246,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In this work we investigated, for the first time, the effect of Plagius flosculosus (L.) Alavi &amp; Heywood, a Sardinian\u2013Corsican endemic plant, on HIV-1 integrase (IN) activity. The phytochemical analysis of the leaves chloroform extract led us to isolate and characterize three compounds (SPK1, SPK2, and SPK3) belonging to the spiroketals, a group of naturally occurring metabolites of phytochemical relevance with interesting biological properties. Due to their structural diversity, these cyclic ketals have attracted the interest of chemists and biologists. SPK1, SPK2, and SPK3 were evaluated here for their ability to inhibit HIV-1 integrase activity in biochemical assays. The results showed that all the compounds inhibited HIV-1 IN activity. In particular, the most active one was SPK3, which interfered in a low molecular range (IC50 of 1.46 \u00b1 0.16 \u00b5M) with HIV-1 IN activity in the presence\/absence of the LEDGF cellular cofactor. To investigate the mechanism of action, the three spiroketals were also tested on HIV-1 RT-associated Ribonuclease H (RNase H) activity, proving to be active in inhibiting this function. Although SPK3 was unable to inhibit viral replication in cell culture, it promoted the IN multimerization. We hypothesize that SPK3 inhibited HIV-1 IN through an allosteric mechanism of action.<\/jats:p>","DOI":"10.3390\/ph16081118","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"1118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HIV-1 Integrase Inhibition Activity by Spiroketals Derived from Plagius flosculosus, an Endemic Plant of Sardinia (Italy) and Corsica (France)"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-2460","authenticated-orcid":false,"given":"Cinzia","family":"Sanna","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Via Sant\u2019Ignazio da Laconi 13, 09123 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-5462","authenticated-orcid":false,"given":"Brigida","family":"D\u2019Abrosca","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies, DiSTABiF University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-7074","authenticated-orcid":false,"given":"Antonio","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies, DiSTABiF University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Giammarino","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-2960","authenticated-orcid":false,"given":"Ilaria","family":"Vicenti","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-8636","authenticated-orcid":false,"given":"Angela","family":"Corona","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS554, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Caredda","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS554, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-0980","authenticated-orcid":false,"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS554, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-7977","authenticated-orcid":false,"given":"Francesca","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS554, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","unstructured":"Fact Sheet\u2014Latest Global and Regional Statistics on the Status of the AIDS Epidemic (2023, April 03). 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