Bioactive phenolic compounds isolated in morus alba leaves as potential inhibitor of Hepatitis C Virus NS3 Protease: A molecular docking approach

Main Article Content

Amaku James Friday
Victor Okezie Ikpeazu
Ifeanyi Otuokere
K. K. Igwe


Communication in Physical Sciences 2020, 5(4): 515-524

Received 25 June 2020/Accepted 29 July 2020

The devastating impact of hepatitis C virus on liver demand the design and development of highly effective therapeutic agents.  Here, we employed computational tools to investigate the inhibitory activity of bioactive phenolic compounds isolated from Morus alba leaves against the hepatitis C virus NS3 protease.  Results obtained from docking study showed indicated that 3,4,5-trimethyoxyphenol-1-O-β-D-rhamnopyranoside had a favourable docking score of -6.6 kcal/mol and was selected as the lead molecule.  The ligand-receptor molecular interaction revealed that 3,4,5-trimethyoxyphenol-1-O-β-D-rhamnopyranoside interacted with HIS55, SER136, SER137, GLY135, LYS134, LEU133, VAL130, ALA155, ALA154, ARG153 and PHE152 at the active site of the target.  The pharmacokinetics and drug-likeness of the lead molecule reveal that 3,4,5-trimethyoxyphenol-1-O-β-D-rhamnopyranoside was soluble in all the class solvent employed for the assay.  Meanwhile, CYP1A2, CYP2C19, CYP2D6, CYP3A4 and CYP2C9 Isoenzymes were not inhibited by 3,4,5-trimethyoxyphenol-1-O-β-D-rhamnopyranoside.  The lead molecule was also noticed to obey Lipinski’s, Egan, Veber and Muegge rules with 0.55 bioavailability score.  Hence, 3,4,5-trimethyoxyphenol-1-O-β-D-rhamnopyranoside have demonstrated drug-like characteristic and may have the capacity to inhibit hepatitis C virus NS3 Protease if subjected to in vitro and in vivo assay.


Download data is not yet available.

Article Details

Author Biographies

Amaku James Friday, Michael Okpara University of Agriculture, Umudike, Abia State Nigeria

Department of Chemistry

Victor Okezie Ikpeazu , Abia State University, Abia State

Department of Biochemistry

Ifeanyi Otuokere , Michael Okpara University of Agriculture, Umudike, Abia State Nigeria

Department of Chemistry

K. K. Igwe , Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria

Departmemt of Veterinary Physiology, Pharmacology and Biochemistry


Akkol, E. K., Süntar, I., Keleş, H., Sezik, E., & Gürler, G. (2015). Bioassay-guided isolation and characterization of wound healer compounds from Morus nigra L.(Moraceae). Records of Natural Products, 9, 4, pp.1-9.

Andreoni, N. (2005). Extraction of mulberry flavonoids for industrial and pharmacological use. Paper presented at the First International Conference on Crop Wild Relative Conservation and Use.

Arabshahi-Delouee, S., & Urooj, A. (2007). Antioxidant properties of various solvent extracts of mulberry (Morus indica L.) leaves. Food chemistry, 102, 4, pp. 1233-1240.

Asano, N., Yamashita, T., Yasuda, K., Ikeda, K., Kizu, H., Kameda, Y., . . . Ryu, K. S. (2001). Polyhydroxylated alkaloids isolated from mulberry trees (Morus alba L.) and silkworms (Bombyx mori L.). Journal of agricultural and food chemistry, 49, 9, pp. 4208-4213.

Chen, C.-C., Liu, L.-K., Hsu, J.-D., Huang, H.-P., Yang, M.-Y., & Wang, C.-J. (2005). Mulberry extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. Food chemistry,91, 4, pp. 601-607.

Choi, E.-M., & Hwang, J.-K. (2005). Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264. 7 macrophages. Fitoterapia, 76, 7-8, pp. 608-613.

Datta, R. (2002). Mulberry cultivation and utilization in India. Mulberry for animal production. FAO animal production and health paper, 147, pp. 45-62.

Enkhmaa, B., Shiwaku, K., Katsube, T., Kitajima, K., Anuurad, E., Yamasaki, M., & Yamane, Y. (2005). Mulberry (Morus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atherosclerotic lesion development in LDL receptor-deficient mice. The Journal of nutrition, 135, 4, pp. (4), 729-734.

Ercisli, S., & Orhan, E. (2007). Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food chemistry, 103, 4, pp. 1380-1384.

Eyduran, S. P., Ercisli, S., Akin, M., Beyhan, O., Geçer, M. K., Eyduran, E., & Erturk, Y. (2015). Organic acids, sugars, vitamin C, antioxidant capacity, and phenolic compounds in fruits of white (Morus alba L.) and black (Morus nigra L.) mulberry genotypes. Journal of Applied Botany and Food Quality, 88, pp.134-138.

Gfeller, D., Grosdidier, A., Wirth, M., Daina, A., Michielin, O., & Zoete, V. (2014). SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic AcidsResearch, 42, W1, pp. W32-W38.

Gupta, G., Imran, K., & Firoz, A. (2013). Anxiolytic activity of moralbosteroid, a steroidal glycoside isolated from Morus alba. Phytopharmacology, 4, pp. 347-353.

Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of cheminformatics, 4, 1, pp. 1-17.

Huang, H.-P., Ou, T.-T., & Wang, C.-J. (2013). Mulberry and its bioactive compounds, the chemoprevention effects and molecular mechanisms in vitro and in vivo. Journal of traditional and complementary medicine, 3, 1, pp. 7-15.

Huang, H.-P., Shih, Y.-W., Chang, Y.-C., Hung, C.-N., & Wang, C.-J. (2008). Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. Journal of agricultural and food chemistry, 56, 19, pp. 9286-9293.

Islam, B., Khan, S. N., Haque, I., Alam, M., Mushfiq, M., & Khan, A. U. (2008). Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba. Journal of antimicrobial chemotherapy, 62, 4, pp. 751-757.

Kang, T. H., Hur, J. Y., Kim, H. B., Ryu, J. H., & Kim, S. Y. (2006). Neuroprotective effects of the cyanidin-3-O-β-d-glucopyranoside isolated from mulberry fruit against cerebral ischemia. Neuroscience letters, 39, 3, pp. 122-126.

Keiser, M. J., Roth, B. L., Armbruster, B. N., Ernsberger, P., Irwin, J. J., & Shoichet, B. K. (2007). Relating protein pharmacology by ligand chemistry. Nature biotechnology, 25, 2, pp. 197-206.

Kim, S. B., Chang, B. Y., Jo, Y. H., Lee, S. H., Han, S.-B., Hwang, B. Y., . . . Lee, M. K. (2013). Macrophage activating activity of pyrrole alkaloids from Morus alba fruits. Journal of ethnopharmacology, 145, 1, pp. 393-396.

Koyuncu, F., Çetinbas, M., & Erdal, İ. (2014). Nutritional constituents of wild-grown black mulberry (Morus nigra L.). Journal of Applied Botany and Food Quality, 87, pp.93-96.

Lee, Y. J., Choi, D. H., Kim, E. J., Kim, H. Y., Kwon, T. O., Kang, D. G., & Lee, H. S. (2011). Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet. The American journal of Chinese medicine, 39, 1, pp. 39-52.

Liu, L.-K., Chou, F.-P., Chen, Y.-C., Chyau, C.-C., Ho, H.-H., & Wang, C.-J. (2009). Effects of mulberry (Morus alba L.) extracts on lipid homeostasis in vitro and in vivo. Journal of agricultural and food chemistry, 57, 16, pp. 7605-7611.

Mahmoud, M. Y. (2013). Natural antioxidants effect of mulberry fruits (Morus nigra and Morus alba L.) on lipids profile and oxidative stress in hypercholestrolemic rats. Pakistan Journal of Nutrition, 12, pp. 665-672.

Memon, A. A., Memon, N., Luthria, D. L., Bhanger, M. I., & Pitafi, A. A. (2010). Phenolic acids profiling and antioxidant potential of mulberry (Morus laevigata W., Morus nigra L., Morus alba L.) leaves and fruits grown in Pakistan. Polish Journal of Food and Nutrition Sciences,60, 1, pp. 25.32

Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of computational chemistry, 19, 14, pp. 1639-1662.

Natić, M. M., Dabić, D. Č., Papetti, A., Akšić, M. M. F., Ognjanov, V., Ljubojević, M., & Tešić, Ž. L. (2015). Analysis and characterisation of phytochemicals in mulberry (Morus alba L.) fruits grown in Vojvodina, North Serbia. Food chemistry, 171, pp. 128-136.

Niidome, T., Takahashi, K., Goto, Y., Goh, S., Tanaka, N., Kamei, K., . . . Kihara, T. (2007). Mulberry leaf extract prevents amyloid beta-peptide fibril formation and neurotoxicity. Neuroreport, 18, 8, pp. 813-816.

Park, K., You, J., Lee, H., Baek, N., & Hwang, J. (2003). Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens. Journal of Ethnopharmacology, 84, 2-3, pp. 181-185.

Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera—a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25, 13, pp. 1605-1612.

Priya, S. (2012). Identification of acetylcholine esterase inhibitors from Morus alba L. leaves. Scholars Research Library, 2, 3pp. 440-444.

Sánchez-Salcedo, E. M., Mena, P., García-Viguera, C., Martínez, J. J., & Hernández, F. (2015). Phytochemical evaluation of white (Morus alba L.) and black (Morus nigra L.) mulberry fruits, a starting point for the assessment of their beneficial properties. Journal of Functional Foods,12, pp. 399-408.

Sánchez, E. M., Calín‐Sánchez, Á., Carbonell‐Barrachina, Á. A., Melgarejo, P., Hernández, F., & Martínez‐Nicolás, J. J. (2014).

Physicochemical characterisation of eight Spanish mulberry clones: processing and fresh market aptitudes. International Journal of Food Science & Technology, 49, 2, pp. 477-483.

Sánchez, M. (2000). World distribution and utilization of mulberry, potencial for animal feeding. FAO Electronic conference on mulberry for animal production (Morus-L).

Shepard, C. W., Finelli, L., & Alter, M. J. (2005). Global epidemiology of hepatitis C virus infection. The Lancet Infectious Diseases, 5, 9, pp. 558-567.

Wang, Y., Xiang, L., Wang, C., Tang, C., & He, X. (2013). Antidiabetic and antioxidant effects and phytochemicals of mulberry fruit (Morus alba L.) polyphenol enhanced extract. PLoS ONE, 8, 7, pp. 71144.

Wattanapitayakul, S. K., Chularojmontri, L., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S., & Bauer, J. A. (2005). Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity. Basic & clinical pharmacology & toxicology, 96, 1, pp. 80-87.

Yang, X., Yang, L., & Zheng, H. (2010). Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food and Chemical Toxicology, 48, 8-9, pp. 2374-2379.