Inhibitory activity of dry ethanol extracts of Artemisia spp. on SARS‐CoV‐2 replication in vitro
https://doi.org/10.18470/1992-1098-2022-4-111-129
Abstract
Aim. In vitro analysis of the inhibitory activity of dry ethanol extracts of some Artemisia spp. growing in the Novosibirsk region for SARS‐CoV‐2 replication.
Materials and Methods. The laboratory strain SARS‐CoV‐2/human/RUS/Nsk‐FRCFTM‐1/2020 was passed on Vero cell culture. Dry ethanol extracts of plant parts (stems, flowers, leaves) of six types of Artemisia were prepared. The types used were: A. vulgaris L.; A. glauca (Pall. Ex Willd.); A. dracunculus L. (from three growth locations); A. absinthium L.; A. frigida Willd.; and A. sieversiana Ehrh. ex Willd. Dry extracts were dissolved in DMSO. In vitro analysis of the inhibitory activity of extracts against SARS‐CoV‐2 (an infectious titer of 103 TCID50/ml) replication was performed in a Vero E6 cell culture. To do this, the method of direct inactivation (neutralization) of virions, as well as schemes of “preventive” and “therapeutic” of cells, were used. Comparison samples were dry ethanol extracts of Inonotus obliquus, Syzygium aromaticum L. and Camellia sinensis L.
Results. Extracts of leaves of Artemisia spp. proved to be most effective in direct inactivation of virions. By equal and decreasing activity these are the species: A. vulgaris; A. dracunculus*; A. absinthium; A. dracunculus***; A. dracunculus**; A. frigidа; A. glauca; and A. sieversiana with a 50% effective concentration of range 1.10±0.24 – 11.72±2.89 μg/ml. Extracts of flowers of A. vulgaris, A.glauca, A. dracunculus*, A. dracunculus**, A. dracunculus***, A. frigida and A. sieversiana also contain biologically active substances which act both destructively on virions and after the virus has entered cells. For extracts of stems consistently high values of EC50 were found for A. glauca (6.84±1.35; 7.81±2.00 and 14.06±3.06 μg/ml) according to the results of three experimental schemes.
Conclusion. The results obtained can become the basis for the development of inexpensive domestic drugs for the treatment and/or prevention of COVID‐19.
About the Authors
Е. I. КаzachinskaiaRussian Federation
Еlena I. Каzachinskaia, Doctor of Biology, Leading Scientist
32‐1, working settlement of Koltsovo, Novosibirsk, Novosibirskaya oblast 630559
Tel. +79095307441
Competing Interests:
The author declares no conflict of interest.
V. D. Romanova
Russian Federation
Valeriya D. Romanova
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
A. V. Ivanоva
Russian Federation
Alla V. Ivanоva
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
А. А. Chepurnov
Russian Federation
Аlexander А. Chepurnov
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
Z. A. Murtazalieva
Russian Federation
Zumrud A. Murtazalieva
Makhachkala
Competing Interests:
The author declares no conflict of interest.
Yu. V. Коnonova
Russian Federation
Yulia V. Коnonova
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
D. N. Shaulo
Russian Federation
Dmitri N. Shaulo
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
V. V. Romanyuk
Russian Federation
Vladimir V. Romanyuk
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
А. М. Shestopalov
Russian Federation
Аlexander М. Shestopalov
Novosibirsk
Competing Interests:
The author declares no conflict of interest.
References
1. Bora K.S., Sharma A. The genus Artemisia: a comprehensive review. Pharmaceutical Biology , 2011, vol. 49, no. 1, pp. 101–109. DOI: 10.3109/13880209.2010.497815
2. Hussain A.A. phylogenetic perspective of antiviral species of the genus Artemisia (Asteraceae-Anthemideae): A proposal of anti SARS-CoV-2 (COVID-19) candidate taxa. J Herb Med., 2022, no. 36, article number: 100601. DOI: 10.1016/j.hermed.2022.100601
3. Leonova T.G. Wormwood – Artemisia L. Flora of the European part of the USSR. St. Petersburg: The Science, 1994, vol. VII, pp. 150–174. (In Russian)
4. Sharifi-Rad J., Herrera-Bravo J., Semwal P., Painuli S., Badoni H., Ezzat Shahira M., Farid M.M., Merghany R.M., Aborehab N.M., Salem M.A, Sen S., Acharya K., Lapava N., Martorell M., Tynybekov B., Calina D., Cho W.C. Artemisia spp.: An Update on Its Chemical Composition, Pharmacological and Toxicological Profiles. Oxid Med Cell Longev. 2022, iss. 2022, article number: 5628601. DOI: 10.1155/2022/5628601
5. Red List. URL: https://www.iucnredlist.org/search/list?taxonomies=115307&searchType=species (Date of application 1.10.2022)
6. Su X.Z., Miller L.H. The discovery of artemisinin and the Nobel Prize in Physiology or Medicine. Science China Life Sciences., 2015, no. 58, pp. 1175–1179. DOI: 10.1007/s11427-015-4948-7
7. Agrawal P.K., Agrawal C., Blunden G. Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment? Molecules., 2022, vol. 27, no. 12, article number: 3828. DOI: 10.3390/molecules27123828
8. Cao R., Hu H., Li Yu., Wang X., Xu M., Liu J., Zhang H., Yan Y., Zhao L., Li W., Zhang T., Xiao D., Guo X., Li Y., Yang J., Hu Z., Wang M., Zhong W. Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. ACS Infect Dis. 2020, vol. 6, no. 9, pp. 2524–2531. DOI: 10.1021/acsinfecdis.0c00522
9. Nie C., Trimpert J., Moon S., Haag R., Gilmore K., Kaufer B.B., Seeberger P.H. In vitro efficacy of Artemisia extracts against SARS-CoV-2. Virol J., 2021, vol. 18(1), article number:182. DOI: 10.1186/s12985-021-01651-8
10. Nair M.S., Huang Y., Fidock D.A., Polyak S.J., Wagoner J., Towler M.J., Weathers P.J. Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants. J Ethnopharmacol., 2021, no. 274, article number: 114016. DOI: 10.1016/j.jep.2021.114016
11. Nair M.S., Huang Y., Fidock D.A., Towler M.J., Weathers P.J. Artemisia annua L. hot-water extracts show potent activity in vitro against Covid-19 variants including delta. J Ethnopharmacol., 2022, no. 284, article number: 114797. DOI: 10.1016/j.jep.2021.114797
12. Nair M.S., Huang Y., Weathers P.J. SARS-CoV-2 omicron variants succumb in vitro to Artemisia annua hot water extracts. BioRxiv. Preprint. 2022. DOI: 10.1101/2022.07.22.501141
13. Dogan K., Erol E., Orhan M.D., Degirmenci Z., Kan T., Gungor A., Yasa B., Avsar T., Cetin Y., Durdagi S., Guzel M. Instant determination of the artemisinin from various Artemisia annua L. extracts by LC-ESI-MS/MS and their in-silico modelling and in vitro antiviral activity studies against SARS-CoV-2. Phytochem Anal., 2022, vol. 33, no. 2, pp. 303–319. DOI: 10.1002/pca.3088
14. Zhurinov M.Zh., Miftakhova A.F., Shustov A.V., Keyer V., Solodova E.V. Inhibitory activity of extracts against coronavirus. Eurasian Journal of Applied Biotechnology. 2022, no. 3, pp. 25–31. (In Russian)
15. Kupferschmidt K. WHO relaunches global drug trial with three new candidates Science. 2021, vol. 373, no. 6555, pp. 606–607. DOI: 10.1126/science.373.6555.606
16. Wang D., Shi C., Alamgir K., Kwon S., Pan L., Zhu Y., Yang X. Global assessment of the distribution and conservation status of a key medicinal plant (Artemisia annua L.): The roles of climate and anthropogenic activities. Sci Total Environ., 2022, no. 821, article number: 153378. DOI: 10.1016/j.scitotenv.2022.153378
17. Konovalov D.A., Khamilonov A.A. Biologically active compounds of Artemisia annua. Essential oil. Pharmacy & Pharmacology, 2016, vol. 4, no. 4, pp. 4–33. (In Russian) DOI: 10.19163/2307-9266-2016-4-4-4-33
18. Zhigzhitzhapova S.V., Dylenova E.P., Gulyaev S.M, Randalova T.E., Taraskin V.V., Tykheev Z.A., Radnaeva L.D. Composition and antioxidant activity of the essential oil of Artemisia annua L Nat Prod Res. 2020, vil. 34(18), pp. 2668–2671. DOI: 10.1080/14786419.2018.1548461
19. Office of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare in the Republic of Dagestan. Available at: https://05.rospotrebnadzor.ru/371/-/asset_publisher/m7XL/content/%D0%BF%D0%BE%D0%BB%D1%8B%D0%BD%D1%8C-%D0%B3%D0%BE%D1%80%D1%8C%D0%BA%D0%B0%D1%8F (accessed 1.10.2022) (In Russian)
20. State Register of Medicines. Available at: http://grls.rosminzdrav.ru. (accessed 04.10.2022) (In Russian)
21. The order of the Rosstandart of the All-Russian classifier of products. Available at: https:/normative.kontur.ru/document?moduleld=1&documenttld=56864 (accessed 1.10.2022). (In Russian)
22. Shalaeva T.M. Features of flavonoid accumulation in wormwood (Artemisia L.) of the forest-steppe zone of Western Siberia. // Abstract of the cand. diss. Novosibirsk, 2007. 18 p. Electronic library of dissertations. Available at: https://www.dissercat.com/content/osobennosti-nakopleniya-flavonoidov-v-polynyakh-artemisia-l-lesostepnoi-zony-zapadnoi-sibiri/read (accessed 1.10.2022). (In Russian)
23. Evseeva S.B., Sysuev B.B. Plant raw material extracts as components of cosmetic products and formulations for topical administration the products range, the production characteristics (review). Pharmacy & Pharmacology, 2016, no. 3, pp. 4–37. (In Russian) DOI: 10.19163/2307-9266-2016-4-3-4-37
24. Krasnoborov I.M. Polyn' – Artemisia L. Opredelitel' rastenii Novosibirskoi oblasti [Wormwood - Artemisia L. Determinant of plants of the Novosibirsk region]. Novosibirsk, Nauka Publ., 2000, pp. 335–339. (In Russian)
25. Teplyakova T.V., Pyankov O.V., Skarnovich M.O., Bormotov N.I., Poteshkina A.L., Ovchinnikova A.S., Kosogova T.A., Magerramova A.V., Markovich N.A., Filippova E.I. An inhibitor of SARS-CoV-2 coronavirus replication based on an aqueous extract of the fungus Inonotus obliquus. Patent of the Russian Federation, no. 2741714C1. (In Russian)
26. Каzachinskaia Е.I., Chepurnov А.А., Коnonova Y.V., Shelemba А.А., Romanyuk V., Magomedov M.G., Shestopalov А.М. Inhibitory activity of tea compositions and their constituent ingredients on SARS-COV-2 replication in vitro. South of Russia: ecology, development, 2022, vol. 17, no. 2, pp. 76–90. (In Russian) DOI: 10.18470/1992-1098-2022-2-76-90
27. Mhatre S., Naik S., Patravale V. A molecular docking study of EGCG and theaflavin digallate with the druggable targets of SARS-CoV-2. Comput Biol Med., 2021, no. 129, article number:104137. DOI: 10.1016/j.compbiomed.2020.104137
28. Mhatre S., Srivastava T., Naik S., Patravale V. Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review. Phytomedicine, 2021, vol. 85, article number: 153286. DOI: 10.1016/j.phymed.2020.153286
29. Ishimoto K., Hatanaka N., Otani S., Maeda S., Xu B., Yasugi M., Moore J.E., Suzuki M., Nakagawa S., Yamasaki S. Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2. Lett Appl Microbiol., 2022, vol. 74, no. 1, pp. 2–7. DOI: 10.1111/lam.13591
30. Chepurnov A.A., Sharshov K.A., Kazachinskaya E.I., Kononova Yu.V., Kazachkova E.A., Khripko O.P., Yurchenko K.S., Alekseev A.Yu., Voevoda M.I., Shestopalov A.M. Antigenic properties of sARs-CoV-2/human/RUs/nsk-FRCFtM-1/2020 coronavirus isolate from a patient in novosibirsk. Journal Infectology, 2020, vol. 12, no. 3, pp. 42–50. (In Russian) DOI: 10.22625/2072-6732-2020-12-3-42-50
31. Kazachinskaia E.I., Chepurnov A.A., Shcherbakov D.N, Kononova Yu.V., Shanshin D.V., Romanova V.D., Khripko O.P., Saroyan T.A., Gulyaeva M.A., Voevoda M.I., Shestopalov A.M. IgG Study of Blood Sera of Patients with COVID-19. Patogens, 2021, vol. 10, no. 11, article number: 1421. DOI: 10.3390/patogens10111421
32. Case J.B., Bailey A.L., Kim A.S., Chen R.E., Diamond M.S. Growth, detection, quantification, and inactivation of SARS-CoV-2. Virology, 2020, no. 548, pp. 39–48. DOI: 10.1016/j.virol.2020.05.015
33. Hassan S.T.S., Berchova-Bimova K., Šudomova M., Malanik M., Smejkal K., Rengasamy K.R.R. In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice. J. Clin. Med., 2018, no. 7, article number: 283. DOI: 10.3390/jcm7090283
34. Fisenko V.P. Rukovodstvo po eksperimental'nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv [Guidelines for the experimental (preclinical) study of new pharmacological substances]. Moscow. 2000, 398 p. (In Russian)
35. Tolah A.M., Altayeb L.M, Alandijany T.A., Dwivedi V.D., El-Kafrawy S.A., Azhar E.I. Computational and In Vitro Experimental Investigations Reveal Anti-Viral Activity of Licorice and Glycyrrhizin against Severe Acute Respiratory Syndrome Coronavirus 2. Pharmaceuticals (Basel), 2021, vol. 14, no. 12, article number: 1216. DOI: 10.3390/ph14121216
36. Teplyakova T.V., Pyankov O.V., Safatov A.S., Ovchinnikova A.S., Kosogova T.A, Skarnovich M.O., Filippova E.I., Poteshkina A.L. Water Extract of the Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Inhibits SARS-CoV-2 Replication in Vero E6 and Vero Cell Culture Experiments. Int J Med Mushrooms., 2022, vol. 24, no. 2, pp. 23–30. DOI: 10.1615/IntJMedMushrooms.2021042012
37. Shahzad F., Anderson D., Najafzadeh M. The Antiviral, Anti-Inflammatory Effects of Natural Medicinal Herbs and Mushrooms and SARS-CoV-2 Infection. Nutrients. 2020, vol. 12, no. 9, article number: 2573. DOI: 10.3390/nu12092573
38. Vicidomini C., Roviello V., Roviello G. Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility. Molecules, 2021, 26, vol. 26, no. 7, article number: 1880. DOI: 10.3390/molecules26071880
39. Zaykovskaya A.V., Gladysheva A.V., Kartashov M.Yu., Taranov O.S., Ovchinnikova A.S., Shipovalov А.V., P’yankov O.V. In vitro Study of Biological Properties of SARS-CoV-2 Coronavirus Strains Related to Various Genetic Variants. Problems of Particularly Dangerous Infections. 2022, no. 1, pp. 94–100. (In Russian) DOI: 10.21055/0370-1069-2022-1-94-100
40. Liu H., Ye F., Sun Q., Liang H., Li C., Li S., Lu R., Huang B., Tan W., Lai L. Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro CoV-2. J Enzyme Inhib Med Chem., 2021, vol. 36, no. 1, pp. 497–503. DOI: 10.1080/14756366.2021.1873977
41. Zannella C., Giugliano R., Chianese A., Buonocore C., Vitale G.A., Sanna G., Sarno F., Manzin A., Nebbioso A., Termolino P., Altucci L., Massimiliano G., de Pascale D., Franci G. Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1. Viruses, 2021, vol. 13, no. 7, article number: 1263. DOI: 10.3390/v13071263
42. Mohamed F.F., Anhlan D., Schöfbänker M., Schreiber A., Classen N., Hensel A., Hempel G., Scholz W., Kühn J., Hrincius E.R., Ludwig S. Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2. Pharmaceuticals (Basel), 2022, vol. 15, no. 5, article number: 530. DOI: 10.3390/ph15050530
43. Trujillo-Correa A.I., Quintero-Gil D.C., Diaz-Castillo F., Quiñones W., Robledo S.M., Martinez-Gutierrez M. In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting. BMC Complement Altern Med., 2019, vol. 19, no. 1, article number: 298. DOI: 10.1186/s12906-019-2695-1
44. Mazurkova N.A., Kukushkina T.A., Vysochina G.I., Ibragimova Zh.B., Lobanova I.E., Filippova E.I., Mazurkov O.Yu., Makarevich E.V., Shishkina L.N., Agafonov A.P. Study of antiherpetic activity of lady’s Mantle (Alchemilla vulgaris L.) extracts. Drug development & registration, 2016, no. 1, pp. 118–127. Available at: :https://www.pharmjournal.ru/jour/article/view/230?locale=ru_RU (accessed 1.10.2022) (In Russian)
45. Mazurkov О.Yu. Antiviral activity, harmlessness and bioavailability of the substance of the candidate anti-inflammatory drug NIOCH-14: PhD Thesis. Koltsovo. 2020. Available at: http://www.vector.nsc.ru/userfiles/files/diss/mazurkov/dmazurkov.pdf (accessed 01.10.2022) (In Russian)
46. García-Lledó A., Gómez-Pavón J., Castillo J.G.D., Hernández-Sampelayo T., Martín-Delgado M.C., Sánchez F.J.M., Martínez-Sellés M., García J.M.M., Guillén S.M., Rodríguez-Artalejo F.J., Ruiz-Galiana J., Cantón R., Ramos P.D.L., García-Botella A., Bouza E. . Pharmacological treatment of COVID-19: an opinion paper Rev Esp Quimioter. 2022, vol. 35, no. 2, pp. 115–130. DOI: 10.37201/req/158.2021
47. da Rocha Matos A., Caetano B.C., de Almeida Filho J.L., de Carvalho Martins J.S.C., de Oliveira M.G.P., das Chagas Sousa T., Horta M.A.P., Siqueira M.M., Fernandez J.H. Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity. Front Microbiol., 2022, no. 13, article number: 828984. DOI: 10.3389/fmicb.2022.828984
48. Prateeksha G., Rana T.S., Ashthana A.K., Barik S.K., Singh B.N. Screening of cryptogamic secondary metabolites as putative inhibitors of SARS-CoV-2 main protease and ribosomal binding domain of spike glycoprotein by molecular docking and molecular dynamics approaches. J Mol Struct., 2021, no. 1240, article number: 130506. DOI: 10.1016/j.molstruc.2021.130506
49. Peng L., Hu Y., Mankowski M., Ren P., Chen R.E., Wei J., Zhao M., Li T., Tripler T., Ye L., Chow R.D., Fang Z., Wu C., Dong M.B., Cook M., Wang G., Clark P., Nelson B., Klein D., Sutton R., Diamond M.S., Wilen C.B., Xiong Y., Chen S. Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. Nat Commun., 2022, vol. 13, no. 1, article number: 1638. DOI: 10.1038/s41467-022-29288-3
50. Logvinenko L.A., Shevchuk O.M., Kravchenko E.N. Introduction study of some species of the Holitone of the collection of aromatic and medicinal plants of the Nikita Botanical Gardens. Agrarnyi vestnik Urala. 2019, no. 4(183), pp. 59–63. (In Russian) DOI: 10.32417/article_5cf9f5c5bfb246.48831055
51. Zhao Z., Li Y., Zhou L., Zhou X., Xie B., Zhang W., Sun J.Prevention and treatment of COVID-19 using Traditional Chinese Medicine: A review. Phytomedicine, 2021, no. 85, article number: 153308. DOI: 10.1016/j.phymed.2020.153308
Review
For citations:
Каzachinskaia Е.I., Romanova V.D., Ivanоva A.V., Chepurnov А.А., Murtazalieva Z.A., Коnonova Yu.V., Shaulo D.N., Romanyuk V.V., Shestopalov А.М. Inhibitory activity of dry ethanol extracts of Artemisia spp. on SARS‐CoV‐2 replication in vitro. South of Russia: ecology, development. 2022;17(4):111‐129. (In Russ.) https://doi.org/10.18470/1992-1098-2022-4-111-129