{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:49:40Z","timestamp":1790380180445,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-75-00117"],"award-info":[{"award-number":["24-75-00117"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-75-00117"],"award-info":[{"award-number":["24-75-00117"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The composition of low-polarity extracts obtained by sequential extraction of the aerial parts of Rhododendron adamsii Rehd. with hexane and methyl tert-butyl ether (MTBE) was investigated using GC-MS. The hexane extract was dominated by non-polar components: squalene, n-alkanes (nonacosane, hentriacontane), sesquiterpenes (trans-nerolidol, spathulenol, \u03b2-farnesene), and \u03b2-sitosterol. The subsequent MTBE extract was enriched in more polar lipids, primarily free triterpenic acids (ursolic and oleanolic acids). A critical finding was the complete absence of diterpene grayanotoxins in all tested extracts, confirming the safety of the non-polar extraction approach. In bioactivity assays, the total hexane extract demonstrated potent inhibitory activity against the SARS-CoV-2 main protease (3CLpro) with IC50 values of 0.0125\u20130.025 mg\/mL, only one order of magnitude higher than the reference inhibitor disulfiram. Fractionation revealed that the activity was distributed among free acids, bound acids, and the unsaponifiable residue, indicating a multicomponent mechanism. Importantly, none of the samples inhibited HIV-1 protease (IC50 &gt; 0.1 mg\/mL), demonstrating selectivity for the cysteine protease 3CLpro over the aspartyl protease of HIV-1. These results highlight that sequential non-polar extraction of R. adamsii provides a grayanotoxin-free lipophilic complex with selective anti-SARS-CoV-2 protease activity, paving the way for bioactivity-guided identification of individual inhibitors.<\/jats:p>","DOI":"10.3390\/molecules31122090","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T03:01:27Z","timestamp":1781492487000},"page":"2090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["How to Turn a Poisonous Plant into Medicine: Non-Polar Extracts of Rhododendron adamsii (Sagan Dalya) Are Free of Grayanotoxins and Inhibit the SARS-CoV-2 Main Protease"],"prefix":"10.3390","volume":"31","author":[{"given":"Tatiana P.","family":"Kukina","sequence":"first","affiliation":[{"name":"Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan A.","family":"Elshin","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ol\u2019ga I.","family":"Sal\u2019nikova","sequence":"additional","affiliation":[{"name":"Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-6335","authenticated-orcid":false,"given":"Svetlana V.","family":"Belenkaya","sequence":"additional","affiliation":[{"name":"Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia"},{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-4719","authenticated-orcid":false,"given":"Evgeniia A.","family":"Kolosova","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia"},{"name":"Center for Recombinant Technologies, Altay State University, 656049 Barnaul, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Volosnikova","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria O.","family":"Shchegolkova","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-4453","authenticated-orcid":false,"given":"Dmitry N.","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia"},{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia"},{"name":"Center for Recombinant Technologies, Altay State University, 656049 Barnaul, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","unstructured":"Budantsev, A.L., and Lesiovskaya, E.E. 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