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Article

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

by
Tatiana P. Kukina
1,*,
Ivan A. Elshin
2,
Ol’ga I. Sal’nikova
1,
Svetlana V. Belenkaya
1,3,
Evgeniia A. Kolosova
3,4,
Ekaterina A. Volosnikova
3,
Victoria O. Shchegolkova
3 and
Dmitry N. Shcherbakov
1,3,4
1
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
2
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
3
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Novosibirsk, Russia
4
Center for Recombinant Technologies, Altay State University, 656049 Barnaul, Russia
*
Author to whom correspondence should be addressed.
Molecules 2026, 31(12), 2090; https://doi.org/10.3390/molecules31122090 (registering DOI)
Submission received: 6 May 2026 / Revised: 31 May 2026 / Accepted: 9 June 2026 / Published: 14 June 2026
(This article belongs to the Special Issue Advancement in Phytochemistry and Pharmacology of Medicinal Plants)
Review Reports Versions Notes

Abstract

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, β-farnesene), and β-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 0.0125–0.025 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 > 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.
Keywords: Rhododendron adamsii; grayanotoxins; ursolic acid; oleanolic acid; triterpenic acids; 3CL protease; SARS-CoV-2; GC-MS Rhododendron adamsii; grayanotoxins; ursolic acid; oleanolic acid; triterpenic acids; 3CL protease; SARS-CoV-2; GC-MS

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MDPI and ACS Style

Kukina, T.P.; Elshin, I.A.; Sal’nikova, O.I.; Belenkaya, S.V.; Kolosova, E.A.; Volosnikova, E.A.; Shchegolkova, V.O.; Shcherbakov, D.N. 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. Molecules 2026, 31, 2090. https://doi.org/10.3390/molecules31122090

AMA Style

Kukina TP, Elshin IA, Sal’nikova OI, Belenkaya SV, Kolosova EA, Volosnikova EA, Shchegolkova VO, Shcherbakov DN. 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. Molecules. 2026; 31(12):2090. https://doi.org/10.3390/molecules31122090

Chicago/Turabian Style

Kukina, Tatiana P., Ivan A. Elshin, Ol’ga I. Sal’nikova, Svetlana V. Belenkaya, Evgeniia A. Kolosova, Ekaterina A. Volosnikova, Victoria O. Shchegolkova, and Dmitry N. Shcherbakov. 2026. "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" Molecules 31, no. 12: 2090. https://doi.org/10.3390/molecules31122090

APA Style

Kukina, T. P., Elshin, I. A., Sal’nikova, O. I., Belenkaya, S. V., Kolosova, E. A., Volosnikova, E. A., Shchegolkova, V. O., & Shcherbakov, D. N. (2026). 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. Molecules, 31(12), 2090. https://doi.org/10.3390/molecules31122090

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