anadolu klin Anatolian Clinic the Journal of Medical Sciences 2149-5254 2458-8849 Hayat Sağlık ve Sosyal Hizmetler Vakfı 10.21673/anadoluklin.724210 Health Care Administration Sağlık Kurumları Yönetimi Koronavirüs Pandemisi ve Türkiye’nin Bazı Şifalı Bitkileri Coronavirus Pandemic and Some Turkish Medicinal Plants https://orcid.org/0000-0002-0630-0106 Şekeroğlu Nazım Kilis 7 Aralık Üniversitesi https://orcid.org/0000-0002-4856-0221 Gezici Sevgi KİLİS 7 ARALIK ÜNİVERSİTESİ 03 20 2020 25 Special Issue on COVID 19 163 182 04 20 2020 05 10 2020 Copyright © 1933, Anadolu Kliniği Tıp Bilimleri Dergisi 1933 Anadolu Kliniği Tıp Bilimleri Dergisi

Çin'de başlayan ve pek çok ülkeyeyayılan Covid-19, ‘Koronavirüs Pandemisi’ olarak dünya çapında bütün insanlığıtehdit eden bir salgın hastalık haline gelmiştir. Virüsün insandan insana hızlıcabulaşması ve yüksek ölüm oranına sahip olması, standart terapi protokolleriningeliştirilmesi ve onaylanması için acil bir ihtiyaç ortaya çıkarmıştır. Etkilitedavi stratejilerinin geliştirilebilmesi için; virüsün yapısal özellikleri,biyolojisi ve konak hücredeki enfeksiyon mekanizmaları tam olarak bilinmelidir.Şimdiye kadar, Kovid-19'un tam bir etkili tedavisi bilinmemekle birlikte,olası antiviral ilaçların klinik deneme ve değerlendirmeleri devam etmektedir. Tıbbi bitkiler glikozitler, saponinler,flavonoidler, proantosiyanidinler, terpenoidler, fenil propanoidler, tanenler,reçineler, lignanlar, sülfitler, polifenolikler, kumarinler, furil bileşikleri,alkaloidler ve uçucu yağlar olmak üzere çok çeşitli aktif fitokimyasalbileşikler ihtiva ettiklerinden dolayı pek çok hastalıkta olduğu gibi viralkaynaklı hastalıklarda da konakçının bağışıklık sistemini güçlendirerekantiviral etki göstermektedir. Yaygın olarak kullanılan bazı yenilebilir yabanibitkilerin, baharatların ve bitkisel çayların çeşitli virüslere karşı güçlü antiviralaktivite gösterdikleri dahası, bunlardan bazılarının farklı tür koronavirüskaynaklı hastalıklarda da kullanılma potansiyelinde olan fito-antiviral ajanlaroldukları önceki çalışmalarda ortaya konulmuştur. Bu derlemede ise; bağışıklıksistemini güçlendirici, hastalıklara karşı koruyucu ve tedavi edici olarakTürkiye’de geleneksel kullanıma sahip olan laden türleri (Cistus spp.), bazı kekik türleri (Origanum, Thymus ve Thymbra),meyan kökü (Glycyrrhiza glabra L.) vezeytin yaprağı (Olea europea L.)bitki türleri ve bunlardan elde edilecek biyoaktif bileşiklerin koronavirüsenfeksiyonları ile mücadelede bitkisel kaynaklı doğal terapötikler olarakkullanılma potansiyelleri güncel literatür bilgileri ışığında sunulmuştur.

Covid-19, emerging in China andspreading to many countries, has become an epidemic disease that threatens allhumanity worldwide as 'Coronavirus Pandemic'. Therapid transmission of the virus from person to person and its high mortalityrate create an urgent need for development and validation of standard therapyprotocols. In order to develop efficient treatment strategies, the structuralfeatures, biology of the virus and the mechanisms of infection in the host cellmust be fully known. So far, the exact effective treatment of Covid-19 has notbeen revealed, but clinical trials and evaluations of possible antiviral drugsare ongoing.Since medicinal plants have a widevariety of bioactive phytochemical compounds such as glycosides, saponins,flavonoids, proanthocyanidins, terpenoids, phenylpropanoids, tannins, resins,lignanes, sulfides, polyphenolics, coumarins, furyl compounds, alkaloids andessential oils, they exhibit antiviral effects by strengthening the immunesystem of the host in diseases of viral origin, as well as they are useful formany diseases. Previous scientific studies showed that commonly used wildedible plants, spices and herbal teas possess strong antiviral activitiesagainst various viruses; moreover, some of them have also been proven to beused for different types of coronavirus-origine diseases as potentialphyto-antiviral agents. In this review, having traditionalmedicinal uses in Turkey, some medicinal plants like cistus species (Cistus spp.), some kekik species (Origanum, Thymus and Thymbra), liquorice root (Glycyrrhizaglabra L.), olive leaf (Olea europeaL.) and their bioactive compounds, which are immune enhancer, preventive andtherapeutic against diseases as potential natural therapeutics for combattingcoronavirus infections have been presented in the light of currents scientificliterature.

 koronavirüs Covid-19 şifalı bitkiler pandemi antiviral antiviral antiviral antiviral Türkiye Coronavirus COVID-19 medicinal plants pandemic Turkey antiviral antiviral antiviral antiviral [1] Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P., ... & Zhang, Q. (2020). Coronavirus infections and immune responses. Journal of medical virology, 92(4), 424-432. https://doi.org/10.1002/jmv.25685. [2] Phan, T. (2020). Novel coronavirus: From discovery to clinical diagnostics. Infection, Genetics and Evolution, 79, 104211. https://doi.org/10.1016/j.meegid.2020.104211. [3] Pillaiyar, T., Meenakshisundaram, S., & Manickam, M. (2020). Recent discovery and development of inhibitors targeting coronaviruses. Drug Discovery Today. 1-21. https://doi.org/10.1016/j.drudis.2020.01.015. [4] Cheever, F. S., Daniels, J. B., Pappenheimer, A. M., & Bailey, O. T. (1949). A murine virus (JHM) causing disseminated encephalomyelitis with extensive destruction of myelin: I. Isolation and biological properties of the virus. The Journal of experimental medicine, 90(3), 181. https://doi.org/10.1084/jem.90.3.181. [5] Geller, C., Varbanov, M., & Duval, R. E. (2012). Human coronaviruses: insights into environmental resistance and its influence on the development of new antiseptic strategies. Viruses, 4(11), 3044-3068. https://doi.org/10.3390/v4113044. [6] Walsh, E. E., Shin, J. H., & Falsey, A. R. (2013). Clinical impact of human coronaviruses 229E and OC43 infection in diverse adult populations. The Journal of infectious diseases, 208(10), 1634-1642. https://doi.org/10.1093/infdis/jit393. [7] Lau, S. K., Woo, P. C., Yip, C. C., Tse, H., Tsoi, H. W., Cheng, V. C., ... & So, L. Y. (2006). Coronavirus HKU1 and other coronavirus infections in Hong Kong. Journal of clinical microbiology, 44(6), 2063-2071. https://doi.org/10.1128/JCM.02614-05. [8] Park, S. Y., Lee, J. S., Son, J. S., Ko, J. H., Peck, K. R., Jung, Y., ... & Shi, H. (2019). Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. Journal of Hospital Infection, 101(1), 42-46. https://doi.org/10.1016/j.jhin.2018.09.005. [9] Pene, F., Merlat, A., Vabret, A., Rozenberg, F., Buzyn, A., Dreyfus, F., ... & Lebon, P. (2003). Coronavirus 229E-related pneumonia in immunocompromised patients. Clinical infectious diseases, 37(7), 929-932. https://doi.org/10.1086/377612. [10] World Health Organization (WHO, 2014) Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update-as of 20 January. Geneva, Switzerland, WHO. [11] World Health Organization (WHO, 2019) Clinical mamagment of severe acute respiratory infection when MERS-CoV infection is suspected: interim guidance. Available at: http://www.who.int/iris/handle/10665/178529 (Accessed 17 April 2019) 2019. [12] Paraskevis, D., Kostaki, E. G., Magiorkinis, G., Panayiotakopoulos, G., Sourvinos, G., & Tsiodras, S. (2020). Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infection, Genetics and Evolution, 79, 104212. https://doi.org/10.1016/j.meegid.2020.104212. [13] Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., ... & Tai, Y. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(20)30076-X. [14] GISAID (Global Initiative on Sharing All Influenza Data (https://www.gisaid.org/). [15] World Health Organization (WHO, 2020). Novel Coronavirus (2019‐nCoV) situation report‐90 [published online ahead of print April 19, 2020]. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200419-sitrep-90-covid-19.pdf?sfvrsn=551d47fd_2. [16] Xui, J., Shi, P. Y., Li, H., & Zhou, J. (2020). Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential. ACS Infectious Diseases. https://doi.org/10.1021/acsinfecdis.0c00052. [17] Cheng, L., Zheng, W., Li, M., Huang, J., Bao, S., Xu, Q., & Ma, Z. (2020). Citrus Fruits Are Rich in Flavonoids for Immunoregulation and Potential Targeting ACE2. https://www.preprints.org/manuscript/202002.0313/v1. [18] Khalifa, I., Zhu, W., Nafie, M. S., Dutta, K., & Li, C. (2020). Anti-COVID-19 Effects of Ten Structurally Different Hydrolysable Tannins through Binding with the Catalytic-Closed Sites of COVID-19 Main Protease: An In-Silico Approach. https://doi.org/10.20944/preprints202003.0277.v1. [19] Luo, H., Tang, Q. L., Shang, Y. X., Liang, S. B., Yang, M., Robinson, N., & Liu, J. P. (2020). Can Chinese medicine be used for prevention of corona virus disease 2019 (COVID-19)? A review of historical classics, research evidence and current prevention programs. Chinese Journal of Integrative Medicine, 1-8. https://doi.org/10.1007/s11655-020-3192-6. [20] Ni, L., Zhou, L., Zhou, M., Zhao, J., & Wang, D. W. (2020). Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19 in Wuhan. Frontiers of Medicine, 1-5. https://doi.org/10.1007/s11684-020-0757-x. [21] King, A. M., Lefkowitz, E., Adams, M. J., & Carstens, E. B. (Eds.). (2011). Virus taxonomy: ninth report of the International Committee on Taxonomy of Viruses (Vol. 9). Elsevier. [22] Kanwar, A., Selvaraju, S., & Esper, F. (2017). Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen. In Open forum infectious diseases 4(2), 1-6, Oxford University Press. https://doi.org/10.1093/ofid/ofx052. [23] Chan, J. F., Lau, S. K., To, K. K., Cheng, V. C., Woo, P. C., & Yuen, K. Y. (2015). Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clinical microbiology reviews, 28(2), 465-522. https://doi.org/110.1128/CMR.00102-14. [24] Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., ... & Guan, L. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. https://doi.org/10.1016/S0140-6736(20)30566-3. [25] Gorbalenya, A. E., Enjuanes, L., Ziebuhr, J., & Snijder, E. J. (2006). Nidovirales: evolving the largest RNA virus genome. Virus research, 117(1), 17-37. https://doi.org/10.1016/j.virusres.2006.01.017. [26] Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B. J., & Jiang, S. (2009). The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nature Reviews Microbiology, 7(3), 226-236. https://doi.org/10.1038/nrmicro2090. [27] Li, W., Sui, J., Huang, I. C., Kuhn, J. H., Radoshitzky, S. R., Marasco, W. A., ... & Farzan, M. (2007). The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology, 367(2), 367-374. https://doi.org/10.1016/j.virol.2007.04.035. [28] Wu, K., Li, W., Peng, G., & Li, F. (2009). Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. Proceedings of the National Academy of Sciences, 106(47), 19970-19974. https://doi.org/10.1073/pnas.0908837106. [29] Huang, X., Dong, W., Milewska, A., Golda, A., Qi, Y., Zhu, Q. K., ... & Li, W. (2015). Human coronavirus HKU1 spike protein uses O-acetylated sialic acid as an attachment receptor determinant and employs hemagglutinin-esterase protein as a receptor-destroying enzyme. Journal of virology, 89(14), 7202-7213. https://doi.org/10.1128/JVI.00854-15. [30] Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X., Niu, P., ... & Sheng, J. (2020). Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell host & microbe. https://doi.org/10.1016/j.chom.2020.02.001. [31] Bertram, S., Dijkman, R., Habjan, M., Heurich, A., Gierer, S., Glowacka, I., ... & Thiel, V. (2013). TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. Journal of virology, 87(11), 6150-6160. https://doi.org/10.1128/JVI.03372-12. [32] Ul Qamar, M. T., Alqahtani, S. M., Alamri, M. A., & Chen, L. L. (2020). Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. https://doi.org/10.20944/preprints202002.0193.v1. [33] Van Boheemen, S., de Graaf, M., Lauber, C., Bestebroer, T. M., Raj, V. S., Zaki, A. M., ... & Fouchier, R. A. (2012). Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. American Society for Microbiology, 3(6), e00473-12. https://doi.org/10.1128/mBio.00473-12. [34] Karypidou, K., Ribone, S. R., Quevedo, M. A., Persoons, L., Pannecouque, C., Helsen, C., ... & Dehaen, W. (2018). Synthesis, biological evaluation and molecular modeling of a novel series of fused 1, 2, 3-triazoles as potential anti-coronavirus agents. Bioorganic & medicinal chemistry letters, 28(21), 3472-3476. https://doi.org/10.1016/j.bmcl.2018.09.019. [35] Desbois, D., Vaghefi, P., Savary, J., Dussaix, E., & Roque-Afonso, A. M. (2008). Sensitivity of a rapid immuno-chromatographic test for hepatitis C antibodies detection. Journal of clinical virology, 41(2), 129-133. https://doi.org/10.1016/j.jcv.2007.11.002. [36] Ababneh, M., Alrwashdeh, M. Khalifeh, M. (2019). Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice. Veterinary World, 12(10), 1554-1562. https://doi.org/10.14202/vetworld.2019.1554-1562. [37] Stebbing, J., Phelan, A., Griffin, I., Tucker, C., Oechsle, O., Smith, D., & Richardson, P. (2020). COVID-19: combining antiviral and anti-inflammatory treatments. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(20)30132-8. [38] Al-Tawfiq, J. A., & Memish, Z. A. (2015). Managing MERS-CoV in the healthcare setting. Hospital Practice, 43(3), 158-163. https://doi.org/10.1080/21548331.2015.1074029. [39] Yoneyama, M., & Fujita, T. (2010). Recognition of viral nucleic acids in innate immunity. Reviews in medical virology, 20(1), 4-22. https://doi.org/10.1002/rmv.633. [40] Cecere, T. E., Todd, S. M., & LeRoith, T. (2012). Regulatory T cells in arterivirus and coronavirus infections: do they protect against disease or enhance it?. Viruses, 4(5), 833-846. ; https://doi.org/10.3390/v4050833. [41] Gralinski, L. E., Sheahan, T. P., Morrison, T. E., Menachery, V. D., Jensen, K., Leist, S. R., ... & Baric, R. S. (2018). Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. MBio, 9(5), e01753-18. https://doi.org/10.1128/mBio.01753-18. [42] Ying, T., Du, L., Ju, T. W., Prabakaran, P., Lau, C. C., Lu, L., ... & Zheng, B. J. (2014). Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. Journal of virology, 88(14), 7796-7805. https://doi.org/10.1128/JVI.00912-14. [43] Shalhoub, S., Farahat, F., Al-Jiffri, A., Simhairi, R., Shamma, O., Siddiqi, N., & Mushtaq, A. (2015). IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. Journal of Antimicrobial Chemotherapy, 70(7), 2129-2132. https://doi.org/10.1093/jac/dkv085. [44] Barnard, D. L., & Kumaki, Y. (2011). Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy. Future virology, 6(5), 615-631. https://doi.org/10.2217/fvl.11.33. [45] Shen, L., Niu, J., Wang, C., Huang, B., Wang, W., Zhu, N., ... & Tan, W. (2019). High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses. Journal of virology, 93(12), e00023-19. https://doi.org/10.1128/JVI.00023-19. [46] Veljkovic, V., Vergara-Alert, J., Segalés, J., & Paessler, S. (2020). Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. F1000Research, 9(52), 1-12. https://doi.org/10.12688/f1000research.22149.2. [47] Chhikara, B. S., Rathi, B., Singh, J., & Poonam, F. N. U. (2020). Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics. Chemical Biology Letters, 7(1), 63-72. [48] Liu, C., Zhou, Q., Li, Y., Garner, L. V., Watkins, S. P., Carter, L. J., ... & Albaiu, D. (2020). Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. https://doi.org/10.1021/acscentsci.0c00272. [49] D'Cruz, O. J., & Uckun, F. M. (2004). Clinical development of microbicides for the prevention of HIV infection. Current pharmaceutical design, 10(3), 315-336. : https://doi.org/10.2174/1381612043386374. [50] Baytop, T. (1999). Türkiye’de Bitkilerle Tedavi – Geçmişte ve Bugün, Nobel Tıp Kitabevleri, İlaveli II. Baskı, İstanbul. [51] Bown, D. (2004). Encyclopedia of Herbs and Their Uses, The Herb Society of America, 167, 16-18, Darling, Kindersley, London. [52] Politeo, O., Burčul, A.M.F., Carev, I., Kamenjarin, J. (2018). Phytochemical Composition and Antimicrobial Activity of Essential Oils of Wild Growing Cistus species in Croatia. Natural Product Communications. 13(6):771-774. [53] Sahraoui, R., Djellali, S., Chakera, A.N. (2013). Morphological, anatomical, secondary metabolites investigation and physicochemical analysis of Cistus creticus. Pharmacognosy Communications. 3(4):58-63. [54] Gürbüz P., Koşar, M., Güvenalp, Z., Kuruüzüm UZ, A., Demirezer, E.Ö. (2018). Simultaneous determination of selected flavonoids from different Cistus species by HPLC-PDA. Marmara Pharm J. 22(3):405-410. [55] Coode MJE (1988). Cistaceae. P Davis, Mill R, Tan K, (Ed.). Flora of Turkey and the East Aegean Islands. vol. 10, Edinburgh University Press. Edinburgh, UK. 61p [56] TUBİVES (2020). Türkiye Bitkileri Veri Servisi. Son Güncelleme: 20.04.2020. http://www.tubives.com/ [57] Stępień, A., Aebisher, D., Bartusik-Aebisher, D. (2018). Biological properties of “Cistus species”. Eur J Clin Exp Med. 16(2):127–132. doi:10.15584/ejcem.2018.2.8. [58] Kilic, D.D., Siriken, B., Erturk, O., Tanrikulu, G., Gül, M., Başkan, C. (2019). Antibacterial, Antioxidant and DNA Interaction Properties of Cistus creticus L. Extracts. J. Int. Environmental Application & Science, 14(3):110-115. [59] Kalus, U., Kiesewetter, H., Radtke, H. (2010). Effect of CYSTUS052“ and Green Tea on Subjective Symptoms in Patients with Infection of the Upper Respiratory Tract. Phytotheraphy Research. 24:96–100. [60] Güvenç, A., Yıldız, S., Özkan, A.M., Erdurak, C.S., Coşkun, M., Yılmaz, G., Okuyama, T., Okada, Y. (2005). Antimicrobiological Studies on Turkish Cistus Species. Pharmaceutical Biology. 43(2):178–183. [61] Ustun, U., Ozcelik, B., Baykal, T. (2016). Bioactivities of Ethanolic Extract and its Fractions of Cistus laurifolius L. (Cistaceae) and Salvia wiedemannii Boiss. (Lamiaceae) Species. Pharmacognosy Magazine. 2016, 12(45): 82-85 (Supplement 1). [62] Ehrhardt C, Hrincius ER, Korte V, et al. (2007). A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antiviral Res. 76;38-47. [63] Kalus, U., Grigorov, A., Kadecki, O., Jansen, J.P., Kiesewetter, H., Radtke, H. (2009). Cistus incanus (CYSTUS052) for treating patients with infection of the upper respiratory tract A prospective, randomised, placebo-controlled clinical study. Antiviral Research. 84:267–271. [64] Wyk, B.E., Wink, M. (2004). Medicinal Plants of the World, Timber Press. Portland, Oregon. USA [65] AMR (2009). Alternative Medicine Review. Olive Leaf Monograph - Foundational Medicine Review. Volume 14, Number 1. http://www.altmedrev.com/archive/publications/14/1/62.pdf [66] Salih, R. H., Odisho, S. M., Al-Shammari, A. M., & Ibrahim, O. M. S. (2017). Antiviral effects of olea europaea leaves extract and interferon-beta on gene expression of newcastle disease virus. Adv Anim Vet Sci, 5(11), 436-45. [67] Lee-Huang, S., Zhang, L., Huang, P. L., Chang, Y. T., & Huang, P. L. (2003). Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochemical and Biophysical Research Communications, 307(4), 1029-1037. https://doi.org/10.1016/S0006-291X(03)01292-0. [68] Zaher, K. S. (2007). In vitro studies on the antiviral effect of olive leaf against infectious laryngotracheitis virus. Global veterinaria, 1(1), 24-30. [69] Motamedifar, M., Nekoueian, A. A., & Moatari, A. (2007). The effect of hydroalcoholic extract of olive leaves against herpes simplex virus type 1. Iranian Journal of Medical Sciences, 32(4), 222-226. [70] Micol, V., Caturla, N., Pérez-Fons, L., Más, V., Pérez, L., & Estepa, A. (2005). The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV). Antiviral research, 66(2-3), 129-136. https://doi.org/10.1016/j.antiviral.2005.02.005. [71] Knipping, K., Garssen, J., & Van’t Land, B. (2012). An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts. Virology journal, 9(1), 137-144. [72] Fredrickson, W. R. (2000). U.S. Patent No. 6,117,844. Washington, DC: U.S. Patent and Trademark Office. [73] Khan, Y., Panchal, S., Vyas, N., Butani, A., & Kumar, V. (2007). Olea europaea: a phyto-pharmacological review. Pharmacognosy Reviews, 1(1), 114-118. http://www.phcogrev.com [74] Baser, K.H.C., Ozek, T. (1993). Composition of the Essential Oil of Turkish Origanum Species with Commercial Importance. Journal of Essential Oil Research. 5:619-623. [75] Baser K.H.C., Kırımer, N. (2018). Essential Oils of Anatolian Lamiaceae – An Update. Nat. Vol. Essent. Oils (NVEO). 5(4):1-28. [76] Tümen, G., Kırımer, N., Başer, K.H.C. (1995). Composition of the Essential Oils of Thymus Species Growing in Turkey. Khim., Prir., Soedin, 1, 55-60. [77] Kızıl, S., Toncer, O., Dıraz, E., Karaman, S. (2015). Variation of agronomical characteristics and essential oil components of zahter (Thymbra spicata L. var. spicata) populations in semi-arid climatic conditions. Turkish Journal Field Crops. 20(2), 242-251. DOI: 10.17557/tjfc.46517 [78] Zhang, X. L., Guo, Y. S., Wang, C. H., Li, G. Q., Xu, J. J., Chung, H. Y., ... & Wang, G. C. (2014). Phenolic compounds from Origanum vulgare and their antioxidant and antiviral activities. Food chemistry, 152, 300-306. [79] Blank, D. E., de Oliveira Hübner, S., Alves, G. H., Cardoso, C. A. L., Freitag, R. A., & Cleff, M. B. (2019). Chemical Composition and Antiviral Effect of Extracts of Origanum vulgare. Advances in Bioscience and Biotechnology, 10(07), 188. https://doi.org/10.4236/abb.2019.107014 [80] Gilling, D. H., Kitajima, M., Torrey, J. R., & Bright, K. R. (2014). Antiviral efficacy and mechanisms of action of oregano essential oil and its primary component carvacrol against murine norovirus. Journal of applied microbiology, 116(5), 1149-1163. [81] Salah-Fatnassi, K. B. H., Slim-Bannour, A., Harzallah-Skhiri, F., Mahjoub, M. A., Mighri, Z., Chaumont, J. P., & Aouni, M. (2010). Activités antivirale et antioxydante in vitro d'huiles essentielles de Thymus capitatus (L.) Hoffmans. & Link de Tunisie. Acta botanica gallica, 157(3), 433-444. [82] Ertürk, Ö., Tanrıkulu, G. İ., Yavuz, C., Can, Z., & Çakır, H. E. (2017). Chemical compositions, antioxidant and antimicrobial activities of the essential oil and extracts of Lamiaceae family (Ocimum basilicum and Thymbra spicata) from Turkey. International Journal of Secondary Metabolite, 4(3, Special Issue 2), 340-348. [83] Duran, N., Kaya, A., Gulbol Duran, G., Eryilmaz, N. (2012). In vitro antiviral effect of the essential oils of Thymbra spicata L. on Herpes simplex virus type 2. ICAMS 2012 – 4th International Conference on Advanced Materials and Systems. [84] Mamedov, N. A., Egamberdieva, D. (2019). Phytochemical constituents and pharmacological effects of licorice: a review. In Plant and Human Health, Volume 3 (pp. 1-21). Springer, Cham. [85] Fiore, C., Eisenhut, M., Krausse, R., Ragazzi, E., Pellati, D., Armanini, D., & Bielenberg, J. (2008). Antiviral effects of Glycyrrhiza species. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 22(2), 141-148. [86] Crance, J. M., Scaramozzino, N., Jouan, A., & Garin, D. (2003). Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses. Antiviral research, 58(1), 73-79. [87] Huan, C. C., Wang, H. X., Sheng, X. X., Wang, R., Wang, X., & Mao, X. (2017). Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein. Archives of virology, 162(6), 1467-1476. [88] Cinatl, J., Morgenstern, B., Bauer, G., Chandra, P., Rabenau, H., & Doerr, H. W. (2003). Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. The Lancet, 361(9374), 2045-2046. [89] Ianevski, A., Andersen, P. I., Merits, A., Bjørås, M., & Kainov, D. (2019). Expanding the activity spectrum of antiviral agents. Drug discovery today. [90] Nirmala, P., & Selvaraj, T. (2011). Anti-inflammatory and anti-bacterial activities of Glycyrrhiza glabra L. Journal of Agricultural Technology, 7(3), 815-23. [91] Batiha, G. S., Beshbishy, A. M., El-Mleeh, A., Abdel-Daim, M. M., & Devkota, H. P. (2020). Traditional uses, bioactive chemical constituents, and pharmacological and toxicological activities of Glycyrrhiza glabra L. Fabaceae). Biomolecules. 1-21. [92] Sun, Z. G., Zhao, T. T., Lu, N., Yang, Y. A., & Zhu, H. L. (2019). Research Progress of Glycyrrhizic Acid on Antiviral Activity. Mini reviews in medicinal chemistry, 19(10), 826-832. [93] Fiore, C., Eisenhut, M., Ragazzi, E., Zanchin, G., & Armanini, D. (2005). A history of the therapeutic use of liquorice in Europe. Journal of ethnopharmacology, 99(3), 317-324. [94] Yasmin, A. R., Chia, S. L., Looi, Q. H., Omar, A. R., Noordin, M. M., & Ideris, A. (2020). Herbal extracts as antiviral agents. In Feed Additives (pp. 115-132). Academic Press. [95] Ghannad, M. S., Mohammadi, A., Safiallahy, S., Faradmal, J., Azizi, M., & Ahmadvand, Z. (2014). The effect of aqueous extract of Glycyrrhiza glabra on herpes simplex virus 1. Jundishapur journal of microbiology, 7(7). [96] Baltina, L. A., Kondratenko, R. M., Plyasunova, O. A., Pokrovskii, A. G., & Tolstikov, G. A. (2009). Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review). Pharmaceutical chemistry journal, 43(10), 539-548. [97] Ashfaq, U. A., Masoud, M. S., Nawaz, Z., & Riazuddin, S. (2011). Glycyrrhizin as antiviral agent against Hepatitis C Virus. Journal of translational medicine, 9(1), 112. [98] Pastorino, G., Cornara, L., Soares, S., Rodrigues, F., & Oliveira, M. B. P. (2018). Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytotherapy research, 32(12), 2323-2339.