Antiviral Effects of Phytochemicals
Year 2021,
Volume: 9 Issue: 4, 1519 - 1535, 31.07.2021
Tuğba Demir
,
Özlem Akpinar
Abstract
Many scientific studies support that active phytochemicals in plants have therapeutic applications genetically and functionally against various viruses. The antiviral mechanism of these agents can be explained by many mechanisms. Their capacity to protect free radical molecules against oxidative damage, DNA inhibition, inhibition of RNA synthesis and viral growth explain the antiviral mechanism of these agents. Numerous epidemiological and experimental studies have revealed that phytochemicals have promising antiviral activities. The aim of this study is to compile research on the antiviral properties of plant extracts and phytochemicals and their effective antiviral applications.
References
- [1] Gasparini, R., Amicizia, D., Lai, P.L., Panatto, D. Clinical and socioeconomic impact of seasonal and pandemic influenza in adults and the elderly. Human Vaccines and Immunotherapeutics, 8(1), 21-28, 2012.
- [2] Nováková, L., Pavlík, J., Chrenková, L., Martinec, O., Červený, L. Current antiviral drugs and their analysis in biological materials–Part II: Antivirals against hepatitis and HIV viruses. Journal of Pharmaceutical and Biomedical Analysis, 147, 378-399, 2018.
- [3] Lai, C.C., Liu, Y. H., Wang, C.Y., Wang, Y.H., Hsueh, S.C., Yen, M.Y., Ko, W.C., Hsueh, P.R. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2): Facts and myths. Journal of Microbiology, Immunology and Infection, 53, 404-412, 2020.
- [4] Sun, J., He, W.T., Wang, L., Lai, A., Ji, X., Zhai, X., Li, G., Suchard, M. A., Tian, J., Zhou, J., Veit, M., Su, S. COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends in Molecular Medicine, 26(5), 483-495, 2020.
- [5] Sağdıç, O., Kayacan, S., Dertli, E., Arıcı, M. Gıda güvenliği açısından COVID-19 etmeni SARS-CoV-2’nin değerlendirilmesi ve korunma yöntemleri. Avrupa Bilim ve Teknoloji Dergisi, (18), 927-933, 2020.
- [6] Dubey, A.K., Jaisankar, T.J., Thappa, D.M. Clinical and morphological characteristics of herpes zoster in south India. Indian Journal of Dermatology, 50(4), 203,2005.
- [7] Ben-Shabat, S., Yarmolinsky, L., Porat, D., Dahan, A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Delivery and Translational Research, 10:354–367, 2019.
- [8] De Clercq, E., Li, G. Approved antiviral drugs over the past 50 years. Clinical Microbiology Reviews, 29(3), 695-747, 2016.
- [9] Johari, J., Kianmehr, A., Mustafa, M.R., Abubakar, S., Zandi, K. Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. International Journal of Molecular Sciences, 13(12), 16785-16795, 2012.
- [10] Küçük, A., Yıldırım, Y. Antiviral İlaçlar. Etlik Veteriner Mikrobiyoloji Dergisi, 30(1), 100-108, 2019.
- [11] Lai, C.L., Gane, E., Liaw, Y.F., Hsu, C.W., Thongsawat, S., Wang, Y., Naoumov, N.V. Telbivudine versus lamivudine in patients with chronic hepatitis B. New England Journal of Medicine, 357(25), 2576-2588, 2007.
- [12] Kamali A., Holodniy M. Influenza treatment and prophylaxis with neuraminidase inhibitors: a review. Infection and Drug Resistance. 6, 187-198, 2013.
- [13] Sancho-Ruiz A., Sheldon J., Soriano V. Telbivudine: a new option fort he treatment of chronic hepatitis B. Expert Opinion on Biological Therapy, 7, 751-761, 2007.
- [14] Soltan, M.M., Zaki, A.K. Antiviral screening of forty-two Egyptian medicinal plants. Journal of Ethnopharmacology, 126(1), 102-107, 2009.
- [15] Brijesh, S., Daswani, P., Tetali, P., Antia, N., Birdi, T. Studies on the antidiarrhoeal activity of Aegle marmelos unripe fruit: Validating its traditional usage. BMC Complementary and Alternative Medicine, 9(1), 47-59, 2009.
- [16] Gunjan, M., Naing, T.W., Saini, R.S., Ahmad, A., Naidu, J.R., Kumar, I. Marketing trends and future prospects of herbal medicine in the treatment of various disease. World Journal of Pharmaceutical Research, 4, 132–155, 2015.
- [17] Biswas, D., Nandy, S., Mukherjee, A., Pandey, D.K., Dey, A. Moringa oleifera Lam. and derived phytochemicals as promising antiviral agents: A review. South African Journal of Botany, 129, 272-282, 2020.
- [18] Naithani, R., Huma, L.C., Holland, L. E., Shukla, D., McCormick, D.L., Mehta, R.G., Moriarty, R.M. Antiviral activity of phytochemicals: a comprehensive review. Mini Reviews in Medicinal Chemistry, 8(11), 1106-1133, 2008.
- [19] Droebner, K., Ehrhardt, C., Poetter, A., Ludwig, S., Planz, O. CYSTUS052, a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice. Antiviral Research, 76(1), 1-10 2007.
- [20] Alfajaro, M.M., Kim, H.J., Park, J.G., Ryu, E.H., Kim, J.Y., Jeong, Y.J., Kwon, H.J. Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea. Virology Journal, 9(1), 310, 2012.
- [21] Choi, J.G., Jin, Y.H., Lee, H., Oh, T.W., Yim, N.H., Cho, W.K., Ma, J.Y. Protective effect of panax notoginseng root water extract against influenza a virus infection by enhancing antiviral interferon-mediated immune responses and natural killer cell activity. Frontiers in Immunology, 8, 1542, 2017.
- [22] Romero-Pérez, G. A., Egashira, M., Harada, Y., Tsuruta, T., Oda, Y., Ueda, F., Inoue, R. Orally administered Salacia reticulata extract reduces H1N1 influenza clinical symptoms in murine lung tissues putatively due to enhanced natural killer cell activity. Frontiers in Immunology, 7, 115, 2016.
- [23] Melikian, G., Mmiro, F., Ndugwa, C., Perry, R., Jackson, J. B., Garrett, E., Semba, R.D. Relation of vitamin A and carotenoid status to growth failure and mortality among Ugandan infants with human immunodeficiency virus. Nutrition, 17(7-8), 567-572, 2001.
- [24] Zakay-Rones, Z., Thom, E., Wollan, T., Wadstein, J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. Journal of International Medical Research, 32(2), 132-140, 2004.
- [25] Zakay-Rones, Z., Varsano, N., Zlotnik, M., Manor, O., Regev, L., Schlesinger, M., Mumcuoglu, M. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. The Journal of Alternative and Complementary Medicine, 1(4), 361-369, 1995.
- [26] Morag, A.M., Mumcuoglu, M., Baybikov, T., Schelsinger, M., Zakay-Rones, Z. Inhibition of sensitive and acyclovir-resistant HSV-1 strains by an elderberry extract in vitro. Z Phytother, 25, 97-98, 1997.
- [27] Fiore, C., Eisenhut, M., Krausse, R., Ragazzi, E., Pellati, D., Armanini, D., Bielenberg, J. Antiviral effects of Glycyrrhiza species. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 22(2), 141-148, 2008.
- [28] Rauš, K., Pleschka, S., Klein, P., Schoop, R., Fisher, P. Effect of an Echinacea-based hot drink versus oseltamivir in influenza treatment: a randomized, double-blind, double-dummy, multicenter, noninferiority clinical trial. Current Therapeutic Research, 77, 66-72, 2015.
- [29] Moradi, M.T., Rafieian-Kopaei, M., Karimi, A. A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus. Avicenna Journal of Phytomedicine, 6(5), 506-512, 2016.
- [30] Lam, S.K., Ng, T.B. A protein with antiproliferative, antifungal and HIV-1 reverse transcriptase inhibitory activities from caper (Capparis spinosa) seeds. Phytomedicine, 16(5), 444-450, 2009.
- [31] Abad, M.J., Guerra, J.A., Bermejo, P., Irurzun, A., Carrasco, L. Search for antiviral activity in higher plant extracts. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 14(8), 604-607, 2000.
- [32] Yarmolinsky, L., Huleihel, M., Zaccai, M., Ben-Shabat, S. Potent antiviral flavone glycosides from Ficus benjamina leaves. Fitoterapia, 83(2), 362-367, 2012.
- [33] Wang, G., Wang, H., Song, Y., Jia, C., Wang, Z., Xu, H. Studies on anti-HSV effect of Ficus carica leaves. Journal of Chinese Medicinal Materials, 27(10), 754-756, 2004.
- [34] Astani, A., Reichling, J., Schnitzler, P. Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro. Chemotherapy, 58(1), 70-77, 2012.
- [35] Parsania, M., Rezaee, M.B., Monavari, S.H., Jaimand, K., Mousavi-Jazayeri, S.M., Razazian, M., Nadjarha, M.H. Antiviral screening of four plant extracts against acyclovir resistant herpes simplex virus type-1. Pakistan Journal of Pharmaceutical Sciences, 30(4), 1407-1411, 2017.
- [36] Karimi, A., Rafieian-Kopaei, M., Moradi, M.T., Alidadi, S. Anti–Herpes Simplex Virus Type-1 Activity and Phenolic Content of Crude Ethanol Extract and Four Corresponding Fractions of Quercus brantii L Acorn. Journal of Evidence-Based Complementary and Alternative Medicine, 22(3), 455-461, 2017.
- [37] Arabzadeh, A.M., Ansari-Dogaheh, M., Sharififar, F., Shakibaie, M., Heidarbeigi, M. Anti herpes simplex-1 activity of a standard extract of Zataria multiflora Boiss. Pakistan Journal of Biological Sciences, 16(4), 180-184, 2013.
- [38] Nakane, H., Ono, K. Differential inhibitory effects of some catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and cellular deoxyribonucleic and ribonucleic acid polymerases. Biochemistry, 29(11), 2841-2845, 1990.
- [39] Karamese, M., Aydogdu, S., Karamese, S. A., Altoparlak, U., Gundogdu, C. Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication. Asian Pacific Journal of Cancer Prevention, 16, 4199-4202, 2015.
- [40] Lv, J.J., Yu, S., Wang, Y.F., Wang, D., Zhu, H.T., Cheng, R.R., Zhang, Y.J. Anti-hepatitis B virus norbisabolane sesquiterpenoids from Phyllanthus acidus and the establishment of their absolute configurations using theoretical calculations. The Journal of Organic Chemistry, 79(12), 5432-5447 2014.
- [41] Callies, O., Bedoya, L. M., Beltrán, M., Muñoz, A., Calderón, P. O., Osorio, A. A., Bazzocchi, I.L. Isolation, structural modification, and HIV inhibition of pentacyclic lupane-type triterpenoids from Cassine xylocarpa and Maytenus cuzcoina. Journal of Natural Products, 78(5), 1045-1055, 2015.
- [42] Rebensburg, S., Helfer, M., Schneider, M., Koppensteiner, H., Eberle, J., Schindler, M., Brack-Werner, R. Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins. Scientific Reports, 6, 20394, 2016.
- [43] Gyuris, A., Szlavik, L., Minarovits, J., Vasas, A., Molnar, J., Hohmann, J. Antiviral activities of extracts of Euphorbia hirta L. against HIV-1, HIV-2 and SIVmac251. in Vivo, 23(3), 429-432, 2009.
- [44] Szlávik, L., Gyuris, Á., Minárovits, J., Forgo, P., Molnár, J., Hohmann, J. Alkaloids from Leucojum vernum and antiretroviral activity of Amaryllidaceae alkaloids. Planta Medica, 70(09), 871-873, 2004.
- [45] Oh, C., Price, J., Brindley, M.A., Widrlechner, M. P., Qu, L., McCoy, J.A., Maury, W. Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L. Virology Journal, 8(1), 188-198, 2011.
- [46] Farsani, M.S., Behbahani, M., Isfahani, H.Z. The effect of root, shoot and seed extracts of the Iranian Thymus L.(family: Lamiaceae) species on HIV-1 replication and CD4 expression. Cell Journal (Yakhteh), 18(2), 255-261, 2016.
- [47] Bedoya, L.M., Abad, M.J., Sánchez-Palomino, S., Alcami, J., Bermejo, P. Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV. Phytomedicine, 17(1), 69-74, 2010.
- [48] Najjari, A.H.A., Rajabi, Z., Marandi, M.V., Dehghan, G. The effect of the hexanic extracts of fig (Ficus carica) and olive (Olea europaea) fruit and nanoparticles of selenium on the immunogenicity of the inactivated avian influenza virus subtype H9N2. In Veterinary Research Forum, 6(3), 227-231, 2015.
- [49] Javed, T., Ashfaq, U.A., Riaz, S., Rehman, S., Riazuddin, S. In-vitro antiviral activity of Solanum nigrum against Hepatitis C Virus. Virology Journal, 8(1), 26-32, 2011.
- [50] Rehman, S., Ijaz, B., Fatima, N., Muhammad, S. A., Riazuddin, S. Therapeutic potential of Taraxacum officinale against HCV NS5B polymerase: In-vitro and In silico study. Biomedicine and Pharmacotherapy, 83, 881-891, 2016.
- [51] Angamuthu, D., Purushothaman, I., Kothandan, S., Swaminathan, R. Antiviral study on Punica granatum L., Momordica charantia L., Andrographis paniculata Nees, and Melia azedarach L., to Human Herpes Virus-3. European Journal of Integrative Medicine, 28, 98-108, 2019.
- [52] Visioli, F., Galli, C., Plasmati, E., Viappiani, S., Hernandez, A., Colombo, C. ve Sala, A., Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation, 102(18): 2169-2171, 2000.
- [53] Fidan, A.F., ve Dündar, Y. Yucca schidigera ve içerdiği saponinler ile fenolik bileşiklerinin, hipokolesterolemik ve antioksidan etkileri. Lalahan Enstitü Dergisi, 47 (2): 31-39, 2007.
- [54] Yuan, Y., Tian, J.M., Xiao, J., Shao, Q., Gao, J.M. Bioactive metabolites isolated from Penicillium sp. YY-20, the endophytic fungus from Ginkgo biloba. Natural Product Research, 28(4), 278-281, 2014.
- [55] Guo, J., Shang, E.X., Duan, J.A., Tang, Y., Qian, D. Determination of ligustilide in the brains of freely moving rats using microdialysis coupled with ultra performance liquid chromatography/mass spectrometry. Fitoterapia, 82(3), 441-445, 2011.
- [56] Orhan, D.D., Özçelik, B., Özgen, S., Ergun, F. Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiological Research, 165(6), 496-504, 2010.
- [57] Park, S., Kim, J.I., Lee, I., Lee, S., Hwang, M.W., Bae, J.Y., Park, M.S. Aronia melanocarpa and its components demonstrate antiviral activity against influenza viruses. Biochemical and Biophysical Research Communications, 440(1), 14-19, 2013.
- [58] Zhang, W., Qiao, H., Lv, Y., Wang, J., Chen, X., Hou, Y., Li, E. Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors. PloS One, 9(10), 1-9, 2014.
- [59] Qian, S., Fan, W., Qian, P., Zhang, D., Wei, Y., Chen, H., Li, X. Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity. Viruses, 7(4), 1613-1626, 2015.
- [60] Shibata, C., Ohno, M., Otsuka, M., Kishikawa, T., Goto, K., Muroyama, R., Koike, K. The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology, 462, 42-48, 2014.
- [61] Hakobyan, A., Arabyan, E., Avetisyan, A., Abroyan, L., Hakobyan, L., Zakaryan, H. Apigenin inhibits African swine fever virus infection in vitro. Archives of Virology, 161(12), 3445-3453, 2016.
- [62] Sithisarn, P., Michaelis, M., Schubert-Zsilavecz, M., Cinatl Jr, J. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Research, 97(1), 41-48, 2013.
- [63] Wu, W., Li, R., Li, X., He, J., Jiang, S., Liu, S., Yang, J. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses, 8(1), 6-24, 2016.
- [64] Ganesan, S., Faris, A.N., Comstock, A.T., Wang, Q., Nanua, S., Hershenson, M.B., Sajjan, U.S. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral research, 94(3), 258-271, 2012.
- [65] Zandi, K., Teoh, B.T., Sam, S.S., Wong, P.F., Mustafa, M.R., AbuBakar, S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virology Journal, 8(1), 560-571, 2011.
- [66] Chiang, L.C., Chiang, W., Liu, M.C., Lin, C.C. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. Journal of Antimicrobial Chemotherapy, 52(2), 194-198, 2003.
- [67] Neznanov, N., Kondratova, A., Chumakov, K.M., Neznanova, L., Kondratov, R., Banerjee, A.K., Gudkov, A. V. Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin. DNA and Cell Biology, 27(4), 191-198, 2008.
- [68] Lee, M., Son, M., Ryu, E., Shin, Y.S., Kim, J.G., Kang, B.W., Kang, H. Quercetin-induced apoptosis prevents EBV infection. Oncotarget, 6(14), 12603- 12624, 2015.
- [69] Li, Y.L., Li, K.M., Su, M.X., Leung, K.T., Chen, Y.W., Zhang, Y.W. Studies on antiviral constituents in stems and leaves of Pithecellibium clypearia. China Journal of Chinese Materia Medica, 31(5), 397-400, 2006.
- [70] Bachmetov, L., Gal‐Tanamy, M., Shapira, A., Vorobeychik, M., Giterman‐Galam, T., Sathiyamoorthy, P., Zemel, R. Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity. Journal of Viral Hepatitis, 19(2), 81-88, 2012.
- [71] Gonzalez, O., Fontanes, V., Raychaudhuri, S., Loo, R., Loo, J., Arumugaswami, V., French, S.W. The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology, 50(6), 1756-1764, 2009.
- [72] Li, B.Q., Fu, T., Dongyan, Y., Mikovits, J.A., Ruscetti, F.W., Wang, J.M. Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochemical and Biophysical Research Communications, 276(2), 534-538, 2000.
- [73] Moghaddam, E., Teoh, B.T., Sam, S.S., Lani, R., Hassandarvish, P., Chik, Z., Zandi, K. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Scientific Reports, 4, 5452-5460, 2014.
- [74] Shi, H., Ren, K., Lv, B., Zhang, W., Zhao, Y., Tan, R.X., Li, E. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice. Scientific Reports, 6, 35851-35863, 2016.
- [75] Jia, Y., Xu, R., Hu, Y., Zhu, T., Ma, T., Wu, H., Hu, L. Anti-NDV activity of baicalin from a traditional Chinese medicine in vitro. Journal of Veterinary Medical Science, 15, 572-593, 2016.
- [76] Huang, H., Zhou, W., Zhu, H., Zhou, P., Shi, X. Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs. Toxicology and Applied Pharmacology, 323, 36-43, 2017.
- [77] Evers, D.L., Chao, C.F., Wang, X., Zhang, Z., Huong, S. M.,Huang, E.S. Human cytomegalovirus-inhibitory flavonoids: studies on antiviral activity and mechanism of action. Antiviral Research, 68(3), 124-134, 2005.
- [78] Konigheim, B.S., Goleniowski, M.E., Contigiani, M.S. Cytotoxicity and antiviral activity of a lignan extracted from Larrea divaricata. Drug Design Reviews-Online, 2(1), 81-83, 2005.
- [79] Demir, T., Akpınar, Ö., Kara, H., Güngör, H. Nar (Punica granatum L.) kabuğunun in vitro antidiyabetik, antienflamatuar, sitotoksik, antioksidan ve antimikrobiyal aktivitesi. Academic Food Journal, 17(1), 61-71, 2019.
- [80] Demir, T., Akpınar, Ö., Kara, H., Güngör, H. Nar kabuğundan antimikrobiyal ve antioksidan aktiviteye sahip fenolik bileşiklerin ekstraksiyon koşullarının optimizasyonu. Gıda, 44(2), 369-382, 2019.
- [81] Huleihel, M., Ishanu, V., Tal, J., Arad, S.M. Antiviral effect of red microalgal polysaccharides on Herpes simplex and Varicella zoster viruses. Journal of Applied Phycology, 13(2), 127-134, 2001.
- [82] Wen, C.C., Kuo, Y.H., Jan, J.T., Liang, P.H., Wang, S.Y., Liu, H.G., Hou, C.C. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. Journal of Medicinal Chemistry, 50(17), 4087-4095, 2007.
- [83] Bettega, J.M.R., Teixeira, H., Bassani, V.L., Barardi, C.R.M., Simões, C.M.O. Evaluation of the antiherpetic activity of standardized extracts of Achyrocline satureioides. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 18(10), 819-823, 2004.
- [84] Kong, L., Li, S., Liao, Q., Zhang, Y., Sun, R., Zhu, X., Zhu, Y. Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity. Antiviral Research, 98(1), 44-53, 2013.
- [85] Zhao, C H., Xu, J., Zhang, Y.Q., Zhao, L.X., Feng, B. Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives. Chemical and Pharmaceutical Bulletin, 62(8), 764-771, 2014.
- [86] Josling, P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Advances in Therapy, 18(4), 189-193, 2001.
- [87] Wölbling, R.H., Leonhardt, K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine, 1(1), 25-31, 1994.
- [88] Houghton, P.J., Woldemariam, T.Z., Khan, A.I., Burke, A., Mahmood, N. Antiviral activity of natural and semi-synthetic chromone alkaloids. Antiviral Research, 25(3-4), 235-244, 1994.
- [89] Konigheim, B.S., Goleniowski, M.E., Contigiani, M.S. Cytotoxicity and antiviral activity of a lignan extracted from Larrea divaricata. Drug Design Reviews-Online, 2(1), 81-83, 2005.
- [90] Li, X., Liu, Y., Wu, T., Jin, Y., Cheng, J., Wan, C., Shi, W. The antiviral effect of baicalin on enterovirus 71 in vitro. Viruses, 7(8), 4756-4771, 2015.
- [91] Castrillo, J.L., Carrasco, L.U.I.S. Action of 3-methylquercetin on poliovirus RNA replication. Journal of Virology, 61(10), 3319-3321, 1987.
- [92] McMahon, J.B., Currens, M.J., Gulakowski, R.J., Buckheit, R.W., Lackman-Smith, C., Hallock, Y. F., Boyd, M.R. Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms. Antimicrobial Agents and Chemotherapy, 39(2), 484-488, 1995.
- [93] Renard-Nozaki, J., Kim, T., Imakura, Y., Kihara, M., Kobayashi, S. Effect of alkaloids isolated from Amaryllidaceae on herpes simplex virus. Research in Virology, 140, 115-128, 1989.
- [94] Dikici, I., Mehmetoglu, I., Dikici, N., Bitirgen, M., Kurban, S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-α treatment. Clinical Biochemistry, 38(12), 1141-1144, 2005.
- [95] Olivero-Verbel, J., Pacheco-Londoño, L. Structure− activity relationships for the anti-HIV activity of flavonoids. Journal of Chemical İnformation and Computer Sciences, 42(5), 1241-1246, 2002.
- [96] Fortin, H., Tomasi, S., Jaccard, P., Robin, V., Boustie, J. A Prenyloxycoumarin from Psiadia dentata1. Chemical and Pharmaceutical Bulletin, 49(5), 619-621, 2001.
- [97] Wink, M. Potential of DNA Intercalating Alkaloids and Other Plant Secondary Metabolites against SARS-CoV-2 Causing COVID-19. Diversity, 12(5), 175-185, 2020.
- [98] Lyu, S.Y., Rhim, J.Y., Park, W.B. Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. Archives of Pharmacal Research, 28(11), 1293-1301, 2005.
- [99] Naithani, R., Mehta, R.G., Shukla, D., Chandersekera, S.N., Moriarty, R.M. Antiviral activity of phytochemicals: a current perspective. In Dietary Components and Immune Function. Humana Press, Totowa, NJ, pp. 421-468, 2010.
- [100] Kim, B.K., Cho, A.R., Park, D.J. Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W emulsions: In vitro and in vivo evaluations. Food Chemistry, 206, 85-91, 2016.
- [101] Seyfoddin, A., Al-Kassas, R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Development and İndustrial Pharmacy, 39(4), 508-519, 2013.
- [102] Gürbüz, A., Güngör, S., Erdal, M.S. Deriye ilaç uygulanması için transetozomların formülasyonu ve in vitro karakterizasyonu. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2(2), 51-59, 2019.
- [103] Gürsoy, R.N., Çevik, Ö. Kendiliğinden emülsifiye olabilen ilaç taşıyıcı sistemler ve farmasötik alanda uygulamaları. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (2), 151-170, 2011.
Fitokimyasalların Antiviral Etkileri
Year 2021,
Volume: 9 Issue: 4, 1519 - 1535, 31.07.2021
Tuğba Demir
,
Özlem Akpinar
Abstract
Bitkilerdeki aktif fitokimyasalların genetik ve fonksiyonel olarak çeşitli virüslere karşı tedavi edici uygulamalara sahip olduğu birçok çalışmayla desteklenmektedir. Bu ajanların antiviral mekanizması, serbest radikal moleküllerinin oksidatif zararlarına karşı koruma kapasiteleri, DNA'nın inhibisyonu, RNA sentezi veya viral çoğalmanın engellenmesi gibi bir çok mekanizma ile açıklanabilir. Çok sayıda epidemiyolojik ve deneysel çalışma, fitokimyasalların ümit verici antiviral aktivitelere sahip olduğunu ortaya koymaktadır. Bu çalışmanın amacı bitki ekstraktlarının ve fitokimyasalların antiviral özelliklerini ve etkin antiviral uygulamalarına yönelik araştırmaları derlemektir.
References
- [1] Gasparini, R., Amicizia, D., Lai, P.L., Panatto, D. Clinical and socioeconomic impact of seasonal and pandemic influenza in adults and the elderly. Human Vaccines and Immunotherapeutics, 8(1), 21-28, 2012.
- [2] Nováková, L., Pavlík, J., Chrenková, L., Martinec, O., Červený, L. Current antiviral drugs and their analysis in biological materials–Part II: Antivirals against hepatitis and HIV viruses. Journal of Pharmaceutical and Biomedical Analysis, 147, 378-399, 2018.
- [3] Lai, C.C., Liu, Y. H., Wang, C.Y., Wang, Y.H., Hsueh, S.C., Yen, M.Y., Ko, W.C., Hsueh, P.R. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2): Facts and myths. Journal of Microbiology, Immunology and Infection, 53, 404-412, 2020.
- [4] Sun, J., He, W.T., Wang, L., Lai, A., Ji, X., Zhai, X., Li, G., Suchard, M. A., Tian, J., Zhou, J., Veit, M., Su, S. COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends in Molecular Medicine, 26(5), 483-495, 2020.
- [5] Sağdıç, O., Kayacan, S., Dertli, E., Arıcı, M. Gıda güvenliği açısından COVID-19 etmeni SARS-CoV-2’nin değerlendirilmesi ve korunma yöntemleri. Avrupa Bilim ve Teknoloji Dergisi, (18), 927-933, 2020.
- [6] Dubey, A.K., Jaisankar, T.J., Thappa, D.M. Clinical and morphological characteristics of herpes zoster in south India. Indian Journal of Dermatology, 50(4), 203,2005.
- [7] Ben-Shabat, S., Yarmolinsky, L., Porat, D., Dahan, A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Delivery and Translational Research, 10:354–367, 2019.
- [8] De Clercq, E., Li, G. Approved antiviral drugs over the past 50 years. Clinical Microbiology Reviews, 29(3), 695-747, 2016.
- [9] Johari, J., Kianmehr, A., Mustafa, M.R., Abubakar, S., Zandi, K. Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. International Journal of Molecular Sciences, 13(12), 16785-16795, 2012.
- [10] Küçük, A., Yıldırım, Y. Antiviral İlaçlar. Etlik Veteriner Mikrobiyoloji Dergisi, 30(1), 100-108, 2019.
- [11] Lai, C.L., Gane, E., Liaw, Y.F., Hsu, C.W., Thongsawat, S., Wang, Y., Naoumov, N.V. Telbivudine versus lamivudine in patients with chronic hepatitis B. New England Journal of Medicine, 357(25), 2576-2588, 2007.
- [12] Kamali A., Holodniy M. Influenza treatment and prophylaxis with neuraminidase inhibitors: a review. Infection and Drug Resistance. 6, 187-198, 2013.
- [13] Sancho-Ruiz A., Sheldon J., Soriano V. Telbivudine: a new option fort he treatment of chronic hepatitis B. Expert Opinion on Biological Therapy, 7, 751-761, 2007.
- [14] Soltan, M.M., Zaki, A.K. Antiviral screening of forty-two Egyptian medicinal plants. Journal of Ethnopharmacology, 126(1), 102-107, 2009.
- [15] Brijesh, S., Daswani, P., Tetali, P., Antia, N., Birdi, T. Studies on the antidiarrhoeal activity of Aegle marmelos unripe fruit: Validating its traditional usage. BMC Complementary and Alternative Medicine, 9(1), 47-59, 2009.
- [16] Gunjan, M., Naing, T.W., Saini, R.S., Ahmad, A., Naidu, J.R., Kumar, I. Marketing trends and future prospects of herbal medicine in the treatment of various disease. World Journal of Pharmaceutical Research, 4, 132–155, 2015.
- [17] Biswas, D., Nandy, S., Mukherjee, A., Pandey, D.K., Dey, A. Moringa oleifera Lam. and derived phytochemicals as promising antiviral agents: A review. South African Journal of Botany, 129, 272-282, 2020.
- [18] Naithani, R., Huma, L.C., Holland, L. E., Shukla, D., McCormick, D.L., Mehta, R.G., Moriarty, R.M. Antiviral activity of phytochemicals: a comprehensive review. Mini Reviews in Medicinal Chemistry, 8(11), 1106-1133, 2008.
- [19] Droebner, K., Ehrhardt, C., Poetter, A., Ludwig, S., Planz, O. CYSTUS052, a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice. Antiviral Research, 76(1), 1-10 2007.
- [20] Alfajaro, M.M., Kim, H.J., Park, J.G., Ryu, E.H., Kim, J.Y., Jeong, Y.J., Kwon, H.J. Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea. Virology Journal, 9(1), 310, 2012.
- [21] Choi, J.G., Jin, Y.H., Lee, H., Oh, T.W., Yim, N.H., Cho, W.K., Ma, J.Y. Protective effect of panax notoginseng root water extract against influenza a virus infection by enhancing antiviral interferon-mediated immune responses and natural killer cell activity. Frontiers in Immunology, 8, 1542, 2017.
- [22] Romero-Pérez, G. A., Egashira, M., Harada, Y., Tsuruta, T., Oda, Y., Ueda, F., Inoue, R. Orally administered Salacia reticulata extract reduces H1N1 influenza clinical symptoms in murine lung tissues putatively due to enhanced natural killer cell activity. Frontiers in Immunology, 7, 115, 2016.
- [23] Melikian, G., Mmiro, F., Ndugwa, C., Perry, R., Jackson, J. B., Garrett, E., Semba, R.D. Relation of vitamin A and carotenoid status to growth failure and mortality among Ugandan infants with human immunodeficiency virus. Nutrition, 17(7-8), 567-572, 2001.
- [24] Zakay-Rones, Z., Thom, E., Wollan, T., Wadstein, J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. Journal of International Medical Research, 32(2), 132-140, 2004.
- [25] Zakay-Rones, Z., Varsano, N., Zlotnik, M., Manor, O., Regev, L., Schlesinger, M., Mumcuoglu, M. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. The Journal of Alternative and Complementary Medicine, 1(4), 361-369, 1995.
- [26] Morag, A.M., Mumcuoglu, M., Baybikov, T., Schelsinger, M., Zakay-Rones, Z. Inhibition of sensitive and acyclovir-resistant HSV-1 strains by an elderberry extract in vitro. Z Phytother, 25, 97-98, 1997.
- [27] Fiore, C., Eisenhut, M., Krausse, R., Ragazzi, E., Pellati, D., Armanini, D., Bielenberg, J. Antiviral effects of Glycyrrhiza species. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 22(2), 141-148, 2008.
- [28] Rauš, K., Pleschka, S., Klein, P., Schoop, R., Fisher, P. Effect of an Echinacea-based hot drink versus oseltamivir in influenza treatment: a randomized, double-blind, double-dummy, multicenter, noninferiority clinical trial. Current Therapeutic Research, 77, 66-72, 2015.
- [29] Moradi, M.T., Rafieian-Kopaei, M., Karimi, A. A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus. Avicenna Journal of Phytomedicine, 6(5), 506-512, 2016.
- [30] Lam, S.K., Ng, T.B. A protein with antiproliferative, antifungal and HIV-1 reverse transcriptase inhibitory activities from caper (Capparis spinosa) seeds. Phytomedicine, 16(5), 444-450, 2009.
- [31] Abad, M.J., Guerra, J.A., Bermejo, P., Irurzun, A., Carrasco, L. Search for antiviral activity in higher plant extracts. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 14(8), 604-607, 2000.
- [32] Yarmolinsky, L., Huleihel, M., Zaccai, M., Ben-Shabat, S. Potent antiviral flavone glycosides from Ficus benjamina leaves. Fitoterapia, 83(2), 362-367, 2012.
- [33] Wang, G., Wang, H., Song, Y., Jia, C., Wang, Z., Xu, H. Studies on anti-HSV effect of Ficus carica leaves. Journal of Chinese Medicinal Materials, 27(10), 754-756, 2004.
- [34] Astani, A., Reichling, J., Schnitzler, P. Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro. Chemotherapy, 58(1), 70-77, 2012.
- [35] Parsania, M., Rezaee, M.B., Monavari, S.H., Jaimand, K., Mousavi-Jazayeri, S.M., Razazian, M., Nadjarha, M.H. Antiviral screening of four plant extracts against acyclovir resistant herpes simplex virus type-1. Pakistan Journal of Pharmaceutical Sciences, 30(4), 1407-1411, 2017.
- [36] Karimi, A., Rafieian-Kopaei, M., Moradi, M.T., Alidadi, S. Anti–Herpes Simplex Virus Type-1 Activity and Phenolic Content of Crude Ethanol Extract and Four Corresponding Fractions of Quercus brantii L Acorn. Journal of Evidence-Based Complementary and Alternative Medicine, 22(3), 455-461, 2017.
- [37] Arabzadeh, A.M., Ansari-Dogaheh, M., Sharififar, F., Shakibaie, M., Heidarbeigi, M. Anti herpes simplex-1 activity of a standard extract of Zataria multiflora Boiss. Pakistan Journal of Biological Sciences, 16(4), 180-184, 2013.
- [38] Nakane, H., Ono, K. Differential inhibitory effects of some catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and cellular deoxyribonucleic and ribonucleic acid polymerases. Biochemistry, 29(11), 2841-2845, 1990.
- [39] Karamese, M., Aydogdu, S., Karamese, S. A., Altoparlak, U., Gundogdu, C. Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication. Asian Pacific Journal of Cancer Prevention, 16, 4199-4202, 2015.
- [40] Lv, J.J., Yu, S., Wang, Y.F., Wang, D., Zhu, H.T., Cheng, R.R., Zhang, Y.J. Anti-hepatitis B virus norbisabolane sesquiterpenoids from Phyllanthus acidus and the establishment of their absolute configurations using theoretical calculations. The Journal of Organic Chemistry, 79(12), 5432-5447 2014.
- [41] Callies, O., Bedoya, L. M., Beltrán, M., Muñoz, A., Calderón, P. O., Osorio, A. A., Bazzocchi, I.L. Isolation, structural modification, and HIV inhibition of pentacyclic lupane-type triterpenoids from Cassine xylocarpa and Maytenus cuzcoina. Journal of Natural Products, 78(5), 1045-1055, 2015.
- [42] Rebensburg, S., Helfer, M., Schneider, M., Koppensteiner, H., Eberle, J., Schindler, M., Brack-Werner, R. Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins. Scientific Reports, 6, 20394, 2016.
- [43] Gyuris, A., Szlavik, L., Minarovits, J., Vasas, A., Molnar, J., Hohmann, J. Antiviral activities of extracts of Euphorbia hirta L. against HIV-1, HIV-2 and SIVmac251. in Vivo, 23(3), 429-432, 2009.
- [44] Szlávik, L., Gyuris, Á., Minárovits, J., Forgo, P., Molnár, J., Hohmann, J. Alkaloids from Leucojum vernum and antiretroviral activity of Amaryllidaceae alkaloids. Planta Medica, 70(09), 871-873, 2004.
- [45] Oh, C., Price, J., Brindley, M.A., Widrlechner, M. P., Qu, L., McCoy, J.A., Maury, W. Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L. Virology Journal, 8(1), 188-198, 2011.
- [46] Farsani, M.S., Behbahani, M., Isfahani, H.Z. The effect of root, shoot and seed extracts of the Iranian Thymus L.(family: Lamiaceae) species on HIV-1 replication and CD4 expression. Cell Journal (Yakhteh), 18(2), 255-261, 2016.
- [47] Bedoya, L.M., Abad, M.J., Sánchez-Palomino, S., Alcami, J., Bermejo, P. Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV. Phytomedicine, 17(1), 69-74, 2010.
- [48] Najjari, A.H.A., Rajabi, Z., Marandi, M.V., Dehghan, G. The effect of the hexanic extracts of fig (Ficus carica) and olive (Olea europaea) fruit and nanoparticles of selenium on the immunogenicity of the inactivated avian influenza virus subtype H9N2. In Veterinary Research Forum, 6(3), 227-231, 2015.
- [49] Javed, T., Ashfaq, U.A., Riaz, S., Rehman, S., Riazuddin, S. In-vitro antiviral activity of Solanum nigrum against Hepatitis C Virus. Virology Journal, 8(1), 26-32, 2011.
- [50] Rehman, S., Ijaz, B., Fatima, N., Muhammad, S. A., Riazuddin, S. Therapeutic potential of Taraxacum officinale against HCV NS5B polymerase: In-vitro and In silico study. Biomedicine and Pharmacotherapy, 83, 881-891, 2016.
- [51] Angamuthu, D., Purushothaman, I., Kothandan, S., Swaminathan, R. Antiviral study on Punica granatum L., Momordica charantia L., Andrographis paniculata Nees, and Melia azedarach L., to Human Herpes Virus-3. European Journal of Integrative Medicine, 28, 98-108, 2019.
- [52] Visioli, F., Galli, C., Plasmati, E., Viappiani, S., Hernandez, A., Colombo, C. ve Sala, A., Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation, 102(18): 2169-2171, 2000.
- [53] Fidan, A.F., ve Dündar, Y. Yucca schidigera ve içerdiği saponinler ile fenolik bileşiklerinin, hipokolesterolemik ve antioksidan etkileri. Lalahan Enstitü Dergisi, 47 (2): 31-39, 2007.
- [54] Yuan, Y., Tian, J.M., Xiao, J., Shao, Q., Gao, J.M. Bioactive metabolites isolated from Penicillium sp. YY-20, the endophytic fungus from Ginkgo biloba. Natural Product Research, 28(4), 278-281, 2014.
- [55] Guo, J., Shang, E.X., Duan, J.A., Tang, Y., Qian, D. Determination of ligustilide in the brains of freely moving rats using microdialysis coupled with ultra performance liquid chromatography/mass spectrometry. Fitoterapia, 82(3), 441-445, 2011.
- [56] Orhan, D.D., Özçelik, B., Özgen, S., Ergun, F. Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiological Research, 165(6), 496-504, 2010.
- [57] Park, S., Kim, J.I., Lee, I., Lee, S., Hwang, M.W., Bae, J.Y., Park, M.S. Aronia melanocarpa and its components demonstrate antiviral activity against influenza viruses. Biochemical and Biophysical Research Communications, 440(1), 14-19, 2013.
- [58] Zhang, W., Qiao, H., Lv, Y., Wang, J., Chen, X., Hou, Y., Li, E. Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors. PloS One, 9(10), 1-9, 2014.
- [59] Qian, S., Fan, W., Qian, P., Zhang, D., Wei, Y., Chen, H., Li, X. Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity. Viruses, 7(4), 1613-1626, 2015.
- [60] Shibata, C., Ohno, M., Otsuka, M., Kishikawa, T., Goto, K., Muroyama, R., Koike, K. The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology, 462, 42-48, 2014.
- [61] Hakobyan, A., Arabyan, E., Avetisyan, A., Abroyan, L., Hakobyan, L., Zakaryan, H. Apigenin inhibits African swine fever virus infection in vitro. Archives of Virology, 161(12), 3445-3453, 2016.
- [62] Sithisarn, P., Michaelis, M., Schubert-Zsilavecz, M., Cinatl Jr, J. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Research, 97(1), 41-48, 2013.
- [63] Wu, W., Li, R., Li, X., He, J., Jiang, S., Liu, S., Yang, J. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses, 8(1), 6-24, 2016.
- [64] Ganesan, S., Faris, A.N., Comstock, A.T., Wang, Q., Nanua, S., Hershenson, M.B., Sajjan, U.S. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral research, 94(3), 258-271, 2012.
- [65] Zandi, K., Teoh, B.T., Sam, S.S., Wong, P.F., Mustafa, M.R., AbuBakar, S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virology Journal, 8(1), 560-571, 2011.
- [66] Chiang, L.C., Chiang, W., Liu, M.C., Lin, C.C. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. Journal of Antimicrobial Chemotherapy, 52(2), 194-198, 2003.
- [67] Neznanov, N., Kondratova, A., Chumakov, K.M., Neznanova, L., Kondratov, R., Banerjee, A.K., Gudkov, A. V. Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin. DNA and Cell Biology, 27(4), 191-198, 2008.
- [68] Lee, M., Son, M., Ryu, E., Shin, Y.S., Kim, J.G., Kang, B.W., Kang, H. Quercetin-induced apoptosis prevents EBV infection. Oncotarget, 6(14), 12603- 12624, 2015.
- [69] Li, Y.L., Li, K.M., Su, M.X., Leung, K.T., Chen, Y.W., Zhang, Y.W. Studies on antiviral constituents in stems and leaves of Pithecellibium clypearia. China Journal of Chinese Materia Medica, 31(5), 397-400, 2006.
- [70] Bachmetov, L., Gal‐Tanamy, M., Shapira, A., Vorobeychik, M., Giterman‐Galam, T., Sathiyamoorthy, P., Zemel, R. Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity. Journal of Viral Hepatitis, 19(2), 81-88, 2012.
- [71] Gonzalez, O., Fontanes, V., Raychaudhuri, S., Loo, R., Loo, J., Arumugaswami, V., French, S.W. The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology, 50(6), 1756-1764, 2009.
- [72] Li, B.Q., Fu, T., Dongyan, Y., Mikovits, J.A., Ruscetti, F.W., Wang, J.M. Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochemical and Biophysical Research Communications, 276(2), 534-538, 2000.
- [73] Moghaddam, E., Teoh, B.T., Sam, S.S., Lani, R., Hassandarvish, P., Chik, Z., Zandi, K. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Scientific Reports, 4, 5452-5460, 2014.
- [74] Shi, H., Ren, K., Lv, B., Zhang, W., Zhao, Y., Tan, R.X., Li, E. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice. Scientific Reports, 6, 35851-35863, 2016.
- [75] Jia, Y., Xu, R., Hu, Y., Zhu, T., Ma, T., Wu, H., Hu, L. Anti-NDV activity of baicalin from a traditional Chinese medicine in vitro. Journal of Veterinary Medical Science, 15, 572-593, 2016.
- [76] Huang, H., Zhou, W., Zhu, H., Zhou, P., Shi, X. Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs. Toxicology and Applied Pharmacology, 323, 36-43, 2017.
- [77] Evers, D.L., Chao, C.F., Wang, X., Zhang, Z., Huong, S. M.,Huang, E.S. Human cytomegalovirus-inhibitory flavonoids: studies on antiviral activity and mechanism of action. Antiviral Research, 68(3), 124-134, 2005.
- [78] Konigheim, B.S., Goleniowski, M.E., Contigiani, M.S. Cytotoxicity and antiviral activity of a lignan extracted from Larrea divaricata. Drug Design Reviews-Online, 2(1), 81-83, 2005.
- [79] Demir, T., Akpınar, Ö., Kara, H., Güngör, H. Nar (Punica granatum L.) kabuğunun in vitro antidiyabetik, antienflamatuar, sitotoksik, antioksidan ve antimikrobiyal aktivitesi. Academic Food Journal, 17(1), 61-71, 2019.
- [80] Demir, T., Akpınar, Ö., Kara, H., Güngör, H. Nar kabuğundan antimikrobiyal ve antioksidan aktiviteye sahip fenolik bileşiklerin ekstraksiyon koşullarının optimizasyonu. Gıda, 44(2), 369-382, 2019.
- [81] Huleihel, M., Ishanu, V., Tal, J., Arad, S.M. Antiviral effect of red microalgal polysaccharides on Herpes simplex and Varicella zoster viruses. Journal of Applied Phycology, 13(2), 127-134, 2001.
- [82] Wen, C.C., Kuo, Y.H., Jan, J.T., Liang, P.H., Wang, S.Y., Liu, H.G., Hou, C.C. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. Journal of Medicinal Chemistry, 50(17), 4087-4095, 2007.
- [83] Bettega, J.M.R., Teixeira, H., Bassani, V.L., Barardi, C.R.M., Simões, C.M.O. Evaluation of the antiherpetic activity of standardized extracts of Achyrocline satureioides. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 18(10), 819-823, 2004.
- [84] Kong, L., Li, S., Liao, Q., Zhang, Y., Sun, R., Zhu, X., Zhu, Y. Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity. Antiviral Research, 98(1), 44-53, 2013.
- [85] Zhao, C H., Xu, J., Zhang, Y.Q., Zhao, L.X., Feng, B. Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives. Chemical and Pharmaceutical Bulletin, 62(8), 764-771, 2014.
- [86] Josling, P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Advances in Therapy, 18(4), 189-193, 2001.
- [87] Wölbling, R.H., Leonhardt, K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine, 1(1), 25-31, 1994.
- [88] Houghton, P.J., Woldemariam, T.Z., Khan, A.I., Burke, A., Mahmood, N. Antiviral activity of natural and semi-synthetic chromone alkaloids. Antiviral Research, 25(3-4), 235-244, 1994.
- [89] Konigheim, B.S., Goleniowski, M.E., Contigiani, M.S. Cytotoxicity and antiviral activity of a lignan extracted from Larrea divaricata. Drug Design Reviews-Online, 2(1), 81-83, 2005.
- [90] Li, X., Liu, Y., Wu, T., Jin, Y., Cheng, J., Wan, C., Shi, W. The antiviral effect of baicalin on enterovirus 71 in vitro. Viruses, 7(8), 4756-4771, 2015.
- [91] Castrillo, J.L., Carrasco, L.U.I.S. Action of 3-methylquercetin on poliovirus RNA replication. Journal of Virology, 61(10), 3319-3321, 1987.
- [92] McMahon, J.B., Currens, M.J., Gulakowski, R.J., Buckheit, R.W., Lackman-Smith, C., Hallock, Y. F., Boyd, M.R. Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms. Antimicrobial Agents and Chemotherapy, 39(2), 484-488, 1995.
- [93] Renard-Nozaki, J., Kim, T., Imakura, Y., Kihara, M., Kobayashi, S. Effect of alkaloids isolated from Amaryllidaceae on herpes simplex virus. Research in Virology, 140, 115-128, 1989.
- [94] Dikici, I., Mehmetoglu, I., Dikici, N., Bitirgen, M., Kurban, S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-α treatment. Clinical Biochemistry, 38(12), 1141-1144, 2005.
- [95] Olivero-Verbel, J., Pacheco-Londoño, L. Structure− activity relationships for the anti-HIV activity of flavonoids. Journal of Chemical İnformation and Computer Sciences, 42(5), 1241-1246, 2002.
- [96] Fortin, H., Tomasi, S., Jaccard, P., Robin, V., Boustie, J. A Prenyloxycoumarin from Psiadia dentata1. Chemical and Pharmaceutical Bulletin, 49(5), 619-621, 2001.
- [97] Wink, M. Potential of DNA Intercalating Alkaloids and Other Plant Secondary Metabolites against SARS-CoV-2 Causing COVID-19. Diversity, 12(5), 175-185, 2020.
- [98] Lyu, S.Y., Rhim, J.Y., Park, W.B. Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. Archives of Pharmacal Research, 28(11), 1293-1301, 2005.
- [99] Naithani, R., Mehta, R.G., Shukla, D., Chandersekera, S.N., Moriarty, R.M. Antiviral activity of phytochemicals: a current perspective. In Dietary Components and Immune Function. Humana Press, Totowa, NJ, pp. 421-468, 2010.
- [100] Kim, B.K., Cho, A.R., Park, D.J. Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W emulsions: In vitro and in vivo evaluations. Food Chemistry, 206, 85-91, 2016.
- [101] Seyfoddin, A., Al-Kassas, R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Development and İndustrial Pharmacy, 39(4), 508-519, 2013.
- [102] Gürbüz, A., Güngör, S., Erdal, M.S. Deriye ilaç uygulanması için transetozomların formülasyonu ve in vitro karakterizasyonu. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2(2), 51-59, 2019.
- [103] Gürsoy, R.N., Çevik, Ö. Kendiliğinden emülsifiye olabilen ilaç taşıyıcı sistemler ve farmasötik alanda uygulamaları. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (2), 151-170, 2011.