This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their monoterpene components were tested for cytotoxic and antiviral activity against SARS-CoV-2 in infected Vero 76 cells. The results showed that the essential oils of four Mentha species, i.e., M. aquatica L. cv. Veronica, M. pulegium L., M. microphylla K.Koch, and M. x villosa Huds., but also Micromeria thymifolia (Scop.) Fritsch and Ziziphora clinopodioides Lam., and five different monoterpenes, i.e., carvacrol, carvone, 1,8-cineol, menthofuran, and pulegone, inhibited the SARS-CoV-2 replication in the infected cells. However, the antiviral activity varied both among essential oils and monoterpenes. Carvone and carvacrol exhibited moderate antiviral activity with IC50 concentrations of 80.23 ± 6.07 μM and 86.55 ± 12.73 μM, respectively, while the other monoterpenes were less active (IC50 > 100.00 μM). Structure-activity relations of related monoterpenes showed that the presence of keto and hydroxyl groups is associated with the activity of carvone and carvacrol, respectively. Furthermore, the carvone-rich essential oil of M. x villosa had the greatest activity among all active essential oils (IC50 127.00 ± 4.63 ppm) while the other active oils exhibited mild (140 ppm < IC50 < 200 ppm) to weak antiviral activity (IC50 > 200 ppm). Both essential oils and monoterpenes showed limited or no cytotoxicity against Vero 76 cells. Hierarchical cluster analysis showed that the differences in the antiviral activity of essential oils were directly attributed to the antiviral efficacies of their particular single monoterpenes. The findings presented here on the novel antiviral property of plant essential oils and monoterpenes might be used in the development of different measures against SARS-CoV-2.

Centre of Region Haná for Biotechnological and Agricultural Research Czech Advanced Technology and Research Institute Palacky University Olomouc Czechia

Centre of the Region Haná for Biotechnological and Agricultural Research Department of Genetic Resources for Vegetables Medicinal and Special Plants Crop Research Institute Olomouc Czechia

Institute of Molecular and Translational Medicine Czech Advanced Technology and Research Institute Palacky University Olomouc Czechia

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Czechia

Zobrazit více v PubMed

Adams R. P. (2007). Identification of Essential Oil Components by Gas Chromatography/Mass Spectrometry. 4th ed. Carol Stream, IL, USA: Allured Publishing Corporation.

Amorati R., Foti M. C., Valgimigli L. (2013). Antioxidant Activity of Essential Oils. J. Agric. Food Chem. 61, 10835–10847. 10.1021/jf403496k PubMed DOI

Angane M., Swift S., Huang K., Butts C. A., Quek S. Y. (2022). Essential Oils and Their Major Components: An Updated Review on Antimicrobial Activities, Mechanism of Action and Their Potential Application in the Food Industry. Foods 11, 464. 10.3390/foods11030464 PubMed DOI PMC

Baser K. H. C., Sezik E., Tümen G. (1991). Composition of the Essential Oil of Ziziphora Clinopodioides Lam. J. Essent. Oil Res. 3, 237–239. 10.1080/10412905.1991.9697934 DOI

Bassolé I. H. N., Juliani H. R. (2012). Essential Oils in Combination and Their Antimicrobial Properties. Molecules 17, 3989–4006. 10.3390/molecules17043989 PubMed DOI PMC

Canedo-Marroquín G., Saavedra F., Andrade C. A., Berrios R. V., Rodríguez-Guilarte L., Opazo M. C., et al. (2020). SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments. Front. Immunol. 11, 569760. 10.3389/fimmu.2020.569760 PubMed DOI PMC

Castle J., Lis-Balchin M. (2002). “History of Usage of Lavandula Species,” in Lavender: The Genus Lavandula . Editor Lis-Balchin M. (London, UK: Taylor & Francis; ).

Ćavar S., Maksimović M., Šolić M. E., Jerković-Mujkić A., Bešta R. (2008). Chemical Composition and Antioxidant and Antimicrobial Activity of Two Satureja Essential Oils. Food Chem. 111, 648–653. 10.1016/j.foodchem.2008.04.033 DOI

Ćavar Zeljković S., Maksimović M. (2015). Chemical Composition and Bioactivity of Essential Oil from Thymus Species in Balkan Peninsula. Phytochem. Rev. 14, 335–352. 10.1007/s11101-014-9378-9 DOI

Ćavar Zeljković S., Šišková J., Komzáková K., De Diego N., Kaffková K., Tarkowski P. (2021b). Phenolic Compounds and Biological Activity of Selected Mentha Species. Plants (Basel) 10, 550. 10.3390/plants10030550 PubMed DOI PMC

Ćavar Zeljković S., Smékalová K., Kaffková K., Štefelová N. (2021a). Influence of Post-Harvesting Period on Quality of Thyme and Spearmint Essential Oils. J. Appl. Res. Med. Arom. Plants 25, 100335. 10.1016/j.jarmap.2021.100335 DOI

Das A., Pandita D., Jain G. K., Agarwal P., Grewal A. S., Khar R. K., et al. (2021). Role of Phytoconstituents in the Management of COVID-19. Chem. Biol. Interact. 341, 109449. 10.1016/j.cbi.2021.109449 PubMed DOI PMC

Diniz L. R. L., Perez-Castillo Y., Elshabrawy H. A., Filho C. D. S. M. B., de Sousa D. P. (2021). Bioactive Terpenes and Their Derivatives as Potential SARS-CoV-2 Proteases Inhibitors from Molecular Modeling Studies. Biomolecules 11, 74. 10.3390/biom11010074 PubMed DOI PMC

Dušková E., Dušek K., Indrák P., Smékalová K. (2016). Postharvest Changes in Essential Oil Content and Quality of Lavender Flowers. Ind. Crops Prod. 79, 225–231. 10.1016/j.indcrop.2015.11.007 DOI

Dzubak P., Hajduch M., Vydra D., Hustova A., Kvasnica M., Biedermann D., et al. (2006). Pharmacological Activities of Natural Triterpenoids and Their Therapeutic Implications. Nat. Prod. Rep. 23, 394–411. 10.1039/b515312n PubMed DOI

Esmaeili Y., Paidari S., Baghbaderani S. A., Nateghi L., Al-Hassan A. A., Ariffin F. (2022). Essential Oils as Natural Antimicrobial Agents in Postharvest Treatments of Fruits and Vegetables: A Review. J. Food Measure. Characteriz. 16, 507–522. 10.1007/s11694-021-01178-0 DOI

Istifli E. S., Netz P. A., Tepe A. S., Husunet M. T., Sarikurkcu C., Tepe B. (2020). In Silico analysis of the Interactions of Certain Flavonoids with the Receptor-Binding Domain of 2019 Novel Coronavirus and Cellular Proteases and Their Pharmacokinetic Properties. J. Biomol. Struct. Dynam. 40, 2460–2474. 10.1080/07391102.2020.1840444 PubMed DOI PMC

Jamshidi-Kia F., Lorigooini Z., Amini-Khoei H. (2018). Medicinal Plants: Past History and Future Perspective. J. Herbmed. Pharmacol. 7, 1–7. 10.15171/jhp.2018.01 DOI

Kampf G., Brüggemann Y., Kaba H. E. J., Steinmann J., Pfaender S., Scheithauer S., et al. (2020). Potential Sources, Modes of Transmission and Effectiveness of Prevention Measures against SARS-CoV-2. J. Hosp. Infect. 106, 678–697. 10.1016/j.jhin.2020.09.022 PubMed DOI PMC

Kim C. H. (2021). Anti-SARS-CoV-2 Natural Products as Potentially Therapeutic Agents. Front. Pharmacol. 12, 590509. 10.3389/fphar.2021.590509 PubMed DOI PMC

Klempt P., Brzoň O., Kašný M., Kvapilová K., Hubáček P., Briksi A., et al. (2021). Distribution of SARS-CoV-2 Lineages in the Czech republic, Analysis of Data from the First Year of the Pandemic. Microorganisms 9, 1671. 10.3390/microorganisms9081671 PubMed DOI PMC

Leung K., Wu J. T., Liu D., Leung G. M. (2020). First-Wave COVID-19 Transmissibility and Severity in China outside Hubei after Control Measures, and Second-Wave Scenario Planning: A Modelling Impact Assessment. Lancet 395 (10233), 1382–1393. 10.1016/S0140-6736(20)30746-7 PubMed DOI PMC

Mamadalieva N. Z., Hussain H., Xiao J. (2020). Recent Advances in Genus Mentha: Phytochemistry, Antimicrobial Effects, and Food Applications. Food Front. 1, 435–458. 10.1002/fft2.53 DOI

Mei M., Tan X. (2021). Current Strategies of Antiviral Drug Discovery for COVID-19. Front. Mol. Biosci. 8, 671263. 10.3389/fmolb.2021.671263 PubMed DOI PMC

Ozturk S., Ercisli S. (2007). Antibacterial Activity and Chemical Constitutions of Ziziphora Clinopodioides . Food Control 18, 535–540. 10.1016/j.foodcont.2006.01.002 DOI

Panikar S., Shoba G., Arun M., Sahayarayan J. J., Usha Raja Nanthini A., Chinnathambi A., et al. (2021). Essential Oils as an Effective Alternative for the Treatment of COVID-19: Molecular Interaction Analysis of Protease (Mpro) with Pharmacokinetics and Toxicological Properties. J. Infect. Public Health 14, 601–610. 10.1016/j.jiph.2020.12.037 PubMed DOI PMC

Pauli A., Schilcher H. (2004). Specific Selection of Essential Oil Compounds for Treatment of Children's Infection Diseases. Pharmaceuticals 1, 1–30. 10.3390/ph1010001 DOI

Perrino E. V., Valerio F., Gannouchi A., Trani A., Mezzapesa G. (2021). Ecological and Plant Community Implication on Essential Oils Composition in Useful Wild Officinal Species: A Pilot Case Study in Apulia (Italy). Plants (Basel) 10, 574. 10.3390/plants10030574 PubMed DOI PMC

Prusinowska R., Śmigielski K. (2015). Losses of Essential Oils and Antioxidants during the Drying of Herbs and Spices. A Review. Eng. Sci. Tech. 2, 51–62. 10.15611/NIT.2015.2.05 DOI

Salehi B., Stojanović-Radić Z., Matejić J., Sharopov F., Antolak H., Kręgiel D., et al. (2018). Plants of Genus Mentha: From Farm to Food Factory. Plants (Basel) 7, 70. 10.3390/plants7030070 PubMed DOI PMC

Salem M. A., Ezzat S. M. (2021). The Use of Aromatic Plants and Their Therapeutic Potential as Antiviral Agents: A hope for Finding Anti-COVID 19 Essential Oils. J. Essent. Oil Res. 33, 105–113. 10.1080/10412905.2021.1886187 DOI

Šavikin K. P., Menković N. R., Zdunić G. M., Tasić S. R., Ristić M. S., Stević T. R., et al. (2010). Hemical Composition and Antimicrobial Activity of the Essential Oils of Micromeria Thymifolia (Scop.) Fritsch., M. Dalmatica Benth., and Satureja Cuneifolia Ten. And its Secretory Elements. J. Essent. Oil Res. 22, 91–96. 10.1080/10412905.2010.9700271 DOI

Scandorieiro S., de Camargo L. C., Lancheros C. A., Yamada-Ogatta S. F., Nakamura C. V., de Oliveira A. G., et al. (2016). Synergistic and Additive Effect of Oregano Essential Oil and Biological Silver Nanoparticles against Multidrug-Resistant Bacterial Strains. Front. Microbiol. 7, 760. 10.3389/fmicb.2016.00760 PubMed DOI PMC

Schadich E., Kryshchyshyn-Dylevych A., Holota S., Polishchuk P., Džubak P., Gurska S., et al. (2020). Assessing Different Thiazolidine and Thiazole Based Compounds as Antileishmanial Scaffolds. Bioorg. Med. Chem. Lett. 30, 127616. 10.1016/j.bmcl.2020.127616 PubMed DOI

Sharifi-Rad J., Quispe C., Kumar M., Akram M., Amin M., Iqbal M., et al. (2022). Hyssopus Essential Oil: An Update of its Phytochemistry, Biological Activities, and Safety Profile. Oxid. Med. Cel. Longev. 2022, 8442734. 10.1155/2022/8442734 PubMed DOI PMC

Sharifi-Rad J., Sureda A., Tenore G. C., Daglia M., Sharifi-Rad M., Valussi M., et al. (2017). Biological Activities of Essential Oils: From Plant Chemoecology to Traditional Healing Systems. Molecules 22, 70. 10.3390/molecules22010070 PubMed DOI PMC

Sharma K., Guleria S., Razdan V. K., Babu V. (2020). Synergistic Antioxidant and Antimicrobial Activities of Essential Oils of Some Selected Medicinal Plants in Combination and with Synthetic Compounds. Ind. Crops Prod. 154, 112569. 10.1016/j.indcrop.2020.112569 DOI

Shin D., Mukherjee R., Grewe D., Bojkova D., Baek K., Bhattacharya A., et al. (2020). Papain-Like Protease Regulates SARS-CoV-2 Viral Spread and Innate Immunity. Nature 587, 657–662. 10.1038/s41586-020-2601-5 PubMed DOI PMC

Silva J. K. R. D., Figueiredo P. L. B., Byler K. G., Setzer W. N. (2020). Essential Oils as Antiviral Agents. Potential of Essential Oils to Treat Sars-Cov-2 Infection: An In-Silico Investigation. Int. J. Mol. Sci. 21, 3426. 10.3390/ijms21103426 PubMed DOI PMC

Singh I., Kaur P., Kaushal U., Kaur V., Shekhar N. (2022). Essential Oils in Treatment and Management of Dental Diseases. Biointerf. Res. Appl. Chem. 12, 7267–7286. 10.33263/BRIAC126.72677286 DOI

Singla R. K., He X., Chopra H., Tsagkaris C., Shen L., Kamal M. A., et al. (2021). Natural Products for the Prevention and Control of the COVID-19 Pandemic: Sustainable Bioresources. Front. Pharmacol. 12, 758159. 10.3389/fphar.2021.758159 PubMed DOI PMC

Slavkovska V., Jancic R., Bojovic S., Milosavljevic S., Djokovic D. (2001). Variability of Essential Oils of Satureja montana L. And Satureja Kitaibelii Wierzb. Ex Heuff. from the Central Part of the Balkan Peninsula. Phytochemistry 57, 71–76. 10.1016/s0031-9422(00)00458-1 PubMed DOI

Szczepaniak S., Polanska M., Van Assche A., Moloney R., Willems K. A. (2011). The Synergism of Natural Compounds in the Pursuit of Safe and Healthier Food. J. Ind. Microbiol. Biotechnol. 38, 215–220. 10.1007/s10295-010-0822-6 PubMed DOI

Tepe B., Cilkiz M. (2016). A Pharmacological and Phytochemical Overview on Satureja . Pharmaceut. Biol. 54, 375–412. 10.3109/13880209.2015.1043560 PubMed DOI

Torres Neto L., Monteiro M. L. G., Galvan D., Conte-Junior C. A. (2021). An Evaluation of the Potential of Essential Oils against SARS-CoV-2 from In Silico Studies through the Systematic Review Using a Chemometric Approach. Pharmaceuticals (Basel) 14, 1138. 10.3390/ph14111138 PubMed DOI PMC

Tucker A. O. (2007). “ Mentha: Economic Uses,” in Mint: The Genus Mentha . Editor Lawrence B.M. (Boca Raton, FL, USA: CRC Press; ), 519–528.

Vaičiulytė V., Ložienė K., Švedienė J., Raudonienė V., Paškevičius A. (2021). α-Terpinyl Acetate: Occurrence in Essential Oils Bearing Thymus Pulegioides, Phytotoxicity, and Antimicrobial Effects. Molecules 26, 1065. 10.3390/molecules26041065 PubMed DOI PMC

Vidic D., Maksimovic M., Cavar S., Solic M. E. (2009). Comparison of Essential Oil Profiles of Satureja Montana L. And Endemic Satureja Visianii Šilić. J. Essent. Oil Bear. Plants 12, 273–281. 10.1080/0972060X.2009.10643720 DOI

Wang L., Wang D., Wu X., Xu R., Li Y. (2020). Antiviral Mechanism of Carvacrol on HSV-2 Infectivity through Inhibition of RIP3-Mediated Programmed Cell Necrosis Pathway and Ubiquitin-Proteasome System in BSC-1 Cells. BMC Infect. Dis. 20, 832. 10.1186/s12879-020-05556-9 PubMed DOI PMC

Wani A. R., Yadav K., Khursheed A., Rather M. A. (2021). An Updated and Comprehensive Review of the Antiviral Potential of Essential Oils and Their Chemical Constituents with Special Focus on Their Mechanism of Action against Various Influenza and Coronaviruses. Microb. Phatog. 152, 104620. 10.1016/j.micpath.2020.104620 PubMed DOI PMC

WHO (2020). Coronavirus Disease 2019 (COVID-19) Situation Report - 38. Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200227-sitrep-38-covid-19.pdf?sfvrsn=9f98940c_2 (Accessed Feb 28th, 2020).

Zarzuelo A., Crespo E. (2002). “The Medicinal and Non-Medicinal Uses of Thyme,” in Thyme: The Genus Thymus . Editors Stahl-Biskup E., Saez F. (London, UK: Taylor & Francis; ).

Zawislak G. (2016). Essential Oil Composition of Hyssopus Officinalis L. Grown in Poland. J. Essent. Oil Bear. Plants 19, 699–705. 10.1080/0972060X.2014.935034 DOI

Secondary metabolite profiles and anti-SARS-CoV-2 activity of ethanolic extracts from nine genotypes of Cannabis sativa L