{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:01Z","timestamp":1787029261796,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), poses a serious global public health threat for which there is currently no satisfactory treatment. This study examines the efficacy of Biobran\/MGN-3 against SARS-CoV-2. Biobran is an arabinoxylan rice bran that has been shown to significantly inhibit the related influenza virus in geriatric subjects. Here, Biobran\u2019s anti-SARS-CoV-2 activity was assessed using MTT and plaque reduction assays, RT-PCR, ELISA techniques, and measurements of SARS-CoV-2-related gene expression and protein levels. For Vero E6 cells infected with SARS-CoV-2, Biobran reduced the viral load by 91.9% at a dose of 100 \u03bcg\/mL, it reduced viral counts (PFU\/mL) by 90.6% at 50 \u03bcg\/mL, and it exhibited a significant selectivity index (EC50\/IC50) of 22.5. In addition, Biobran at 10 \u03bcg\/mL inhibited papain-like proteinase (PLpro) by 87% and ACE2 SARS-CoV-2 S-protein RBD by 90.5%, and it significantly suppressed SARS-CoV-2 gene expression, down-regulating E-gene and RdRp gene expression by 93% each at a dose of 50 \u03bcg\/mL and inhibiting the E-protein by 91.3%. An in silico docking study was also performed to examine the protein\u2013protein interaction (PPI) between SARS-CoV-2 RBD and DC-SIGN as well as between serine carboxypeptidase and papain-like protease PLpro. Serine carboxypeptidase, an active ingredient in Biobran, was found to interfere with the binding of SARS-CoV-2 to its receptor DC-SIGN on Vero cells, thus preventing the cell entry of SARS-CoV-2. In addition, it impairs the viral replication cycle by binding to PLpro. We conclude that Biobran possesses potent antiviral activity against SARS-CoV-2 in vitro and suggest that Biobran may be able to prevent SARS-CoV-2 infection. This warrants further investigation in clinical trials.<\/jats:p>","DOI":"10.3390\/nu15020453","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T04:06:47Z","timestamp":1673842007000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biobran\/MGN-3, an Arabinoxylan Rice Bran, Protects against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An In Vitro and In Silico Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Mamdooh","family":"Ghoneum","sequence":"first","affiliation":[{"name":"Department of Surgery, Charles R. Drew University of Medicine and Science, 1731 E. 120th Street, Los Angeles, CA 90059, USA"},{"name":"Department of Surgery, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa","family":"Abdulmalek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-0405","authenticated-orcid":false,"given":"Hewida H.","family":"Fadel","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Allied Medical Sciences, Pharos University in Alexandria, Alexandria 21648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.idc.2019.07.001","article-title":"Severe acute respiratory synrome: Historical, epidemiologic, and clinical features","volume":"33","author":"Hui","year":"2019","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7790","DOI":"10.1128\/JVI.01244-13","article-title":"Commentary: Middle East respiratory syndrome coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group","volume":"87","author":"Baker","year":"2013","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106054","DOI":"10.1016\/j.ijantimicag.2020.106054","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A global pandemic and treatment strategies","volume":"56","author":"Sharma","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_4","unstructured":"WHO (2021, October 15). World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard., Available online: https:\/\/covid19.who.int\/."},{"key":"ref_5","first-page":"753","article-title":"Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19)","volume":"96","author":"Umakanthan","year":"2020","journal-title":"Postgrad. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sharma, A., Ahmad Farouk, I., and Lal, S.K. (2021). COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses, 13.","DOI":"10.3390\/v13020202"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1021\/acscentsci.0c01537","article-title":"CD209L\/L-SIGN and CD209\/DC-SIGN Act as Receptors for SARS-CoV-2","volume":"7","author":"Amraei","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-020-2601-5","article-title":"Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity","volume":"587","author":"Shin","year":"2020","journal-title":"Nature"},{"key":"ref_9","unstructured":"(2021, May 30). World Health Organization Draft Landscape and Tracker of COVID-19 Candidate Vaccines. Available online: https:\/\/www.who.int\/publications\/m\/item\/draft-landscape-of-covid-19-candidate-vaccines."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cmi.2021.10.005","article-title":"Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: A narrative review","volume":"28","author":"Fiolet","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kim, Y.S., Kim, B., Kwon, E.B., Chung, H.S., and Choi, J.G. (2022). Mulberrofuran G, a mulberry component, prevents SARS-CoV-2 infection by blocking the interaction between SARS-CoV-2 spike protein S1 receptor-binding domain and human angiotensin-converting enzyme 2 receptor. Nutrients, 14.","DOI":"10.3390\/nu14194170"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, L., and Wang, Z. (2021). Natural products, alone or in combination with FDA-approved drugs, to treat COVID-19 and lung cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060689"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, D., Huang, J., Yeung, A.W.K., Tzvetkov, N.T., Horbanczuk, J.O., Willschke, H., Gai, Z., and Atanasov, A.G. (2020). The significance of natural product derivatives and traditional medicine for COVID-19. Processes, 8.","DOI":"10.3390\/pr8080937"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1015355","DOI":"10.3389\/fimmu.2022.1015355","article-title":"Oral GS-441524 derivatives: Next-generation inhibitors of SARS-CoV-2 RNA-dependent RNA polymerase","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brahmi, F., Vejux, A., Ghzaiel, I., Ksila, M., Zarrouk, A., Ghrairi, T., Essadek, S., Mandard, S., Leoni, V., and Poli, G. (2022). Role of diet and nutrients in SARS-CoV-2 infection: Incidence on oxidative stress, inflammatory status and viral production. Nutrients, 14.","DOI":"10.3390\/nu14112194"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197989","DOI":"10.1016\/j.virusres.2020.197989","article-title":"Natural product-derived phytochemicals as potential agents against coronaviruses: A review","volume":"284","author":"Mani","year":"2020","journal-title":"Virus Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s13659-020-00250-4","article-title":"Natural products as potential leads against coronaviruses: Could they be encouraging structural models against SARS-CoV-2?","volume":"10","author":"Orhan","year":"2020","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109211","DOI":"10.1016\/j.cbi.2020.109211","article-title":"Roles of flavonoids against coronavirus infection","volume":"328","author":"Russo","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cofs.2020.08.004","article-title":"Potential use of polyphenols in the battle against COVID-19","volume":"32","author":"Paraiso","year":"2020","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mohamed, M.E., Tawfeek, N., Elbaramawi, S.S., and Fikry, E. (2022). Agathis robusta Bark Essential Oil Effectiveness against COVID-19: Chemical Composition, In Silico and In Vitro Approaches. Plants, 11.","DOI":"10.3390\/plants11050663"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ali, A.M., and Kunugi, H. (2021). Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies. Molecules, 26.","DOI":"10.3390\/molecules26051232"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197767","DOI":"10.1016\/j.virusres.2019.197767","article-title":"Antiviral activity of Sambucus Formosan Nakai ethanol extract and related phenolic acid constituents against human coronavirus NL63","volume":"273","author":"Weng","year":"2019","journal-title":"Virus Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, C., Zuckerman, D.M., Brantley, S., Sharpe, M., Childress, K., Hoiczyk, E., and Pendleton, A.R. (2014). Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet. Res., 10.","DOI":"10.1186\/1746-6148-10-24"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113438","DOI":"10.1016\/j.indcrop.2021.113438","article-title":"Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro","volume":"165","author":"Boroduske","year":"2021","journal-title":"Ind. Crops Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/ptr.6916","article-title":"Resveratrol inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cultured Vero cells","volume":"35","author":"Yang","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Elsaid, A.F., Agrawal, S., Agrawal, A., and Ghoneum, M. (2021). Dietary Supplementation with Biobran\/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial. Nutrients, 13.","DOI":"10.3390\/nu13114133"},{"key":"ref_27","first-page":"132","article-title":"The orally administration of the Hydrolysis Rice Bran prevents a common cold syndrome for the elderly people based on immunomodulatory function","volume":"20","author":"Tazawa","year":"2003","journal-title":"J. Trad. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1006\/bbrc.1997.8047","article-title":"Anti-HIV activity in vitro of MGN-3, an activated arabinoxylan from rice bran","volume":"243","author":"Ghoneum","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1177\/0394632016674954","article-title":"Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial","volume":"29","author":"Salama","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/01635580701627285","article-title":"In vivo tumor inhibitory effects of nutritional rice bran supplement MGN-3\/Biobran on Ehrlich carcinoma-bearing mice","volume":"60","author":"Noaman","year":"2008","journal-title":"Nutr. Cancer"},{"key":"ref_31","first-page":"5145","article-title":"Arabinoxylan rice bran (MGN-3) enhances the effects of interventional therapies for the treatment of hepatocellular carcinoma: A three year randomized clinical trial","volume":"30","author":"Bang","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_32","first-page":"89","article-title":"Enhancement of human natural killer cell activity by modified arabinoxylan from rice bran (MGN-3)","volume":"14","author":"Ghoneum","year":"1998","journal-title":"Int. J. Immunother."},{"key":"ref_33","first-page":"314","article-title":"Production of tumor necrosis factor alpha and interferon-gamma from human peripheral blood lymphocytes by MGN-3, a modified arabinoxylan from rice bran, and its synergy with interleukin-2 in vitro","volume":"24","author":"Ghoneum","year":"2000","journal-title":"Cancer Detect. Prev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1211\/0022357044922","article-title":"Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3\/Biobran)","volume":"56","author":"Ghoneum","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","first-page":"217","article-title":"NK immunorestoration of cancer patients by, M.G.N.-3.; a modified arabinoxylan rice bran (study of 32 patients followed for up to 4 years)","volume":"Volume III","author":"Klatz","year":"1999","journal-title":"Anti-Aging Medical Therapeutics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00262-012-1344-z","article-title":"MGN-3 arabinoxylan rice bran modulates innate immunity in multiple myeloma patients","volume":"62","author":"Cholujova","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4149\/neo_2009_02_89","article-title":"Biobran-augmented maturation of human monocyte-derived dendritic cells","volume":"56","author":"Cholujova","year":"2009","journal-title":"Neoplasma"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1177\/039463201102400412","article-title":"Activation of human monocyte derived dendritic cells in vitro by the biological response modifier arabinoxylan rice bran (MGN-3\/Biobran)","volume":"24","author":"Ghoneum","year":"2011","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1177\/039463201402700408","article-title":"MGN-3\/biobran enhances generation of cytotoxic CD8+ T cells via upregulation of dec-205 expression on dendritic cells","volume":"27","author":"Ghoneum","year":"2014","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/039463200401700308","article-title":"Augmentation of macrophage phagocytosis by modified arabinoxylan rice bran (MGN-3\/biobran)","volume":"17","author":"Ghoneum","year":"2004","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s11136-019-02286-7","article-title":"The enhancing effects of Biobran\/MGN-3, an arabinoxylan rice bran, on healthy old adults\u2019 health-related quality of life: A randomized, double-blind, placebo-controlled clinical trial","volume":"29","author":"Elsaid","year":"2020","journal-title":"Qual. Life Res."},{"key":"ref_42","first-page":"267","article-title":"The life prolongation and QOL improvement effect of rice bran arabinoxylan derivative (MGN-3. Bio-Bran) for progressive cancer","volume":"14","author":"Takahara","year":"2004","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_43","first-page":"11","article-title":"Antioxidant and Anti-inflammatory Capacity of Ferulic Acid Released from Wheat Bran by Solid-state Fermentation of Aspergillus niger","volume":"32","author":"Yin","year":"2019","journal-title":"Biomed. Environ. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1016\/S0021-9258(19)39176-8","article-title":"Structure of wheat II at 3.5-A resolution. A new class of serine proteinase","volume":"265","author":"Liao","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2314759","DOI":"10.1155\/2018\/2314759","article-title":"Ferulated Arabinoxylans and Their Gels: Functional Properties and Potential Application as Antioxidant and Anticancer Agent","volume":"2018","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"Tai","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1046\/j.1471-4159.1997.69020581.x","article-title":"Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction","volume":"69","author":"Liu","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1128\/AAC.44.3.688-692.2000","article-title":"A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates","volume":"44","author":"Landry","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"104787","DOI":"10.1016\/j.antiviral.2020.104787","article-title":"The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro","volume":"178","author":"Caly","year":"2020","journal-title":"Antiviral Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","article-title":"Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion","volume":"30","author":"Xia","year":"2020","journal-title":"Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/clinchem\/hvaa029","article-title":"Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia","volume":"66","author":"Chu","year":"2020","journal-title":"Clin. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hong, J., Wang, Q., Wu, Q., Chen, J., Wang, X., Wang, Y., Chen, Y., and Xia, N. (2021). Rabbit Monoclonal Antibody Specifically Recognizing a Linear Epitope in the RBD of SARS-CoV-2 Spike Protein. Vaccines, 9.","DOI":"10.3390\/vaccines9080829"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1186\/1471-2105-12-S1-S33","article-title":"iGEMDOCK: A graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis","volume":"12","author":"Hsu","year":"2011","journal-title":"BMC Bioinform."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s12931-021-01698-9","article-title":"Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: Potential for repurposing in COVID-19-like conditions","volume":"22","author":"Gheware","year":"2021","journal-title":"Respir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s10096-020-03913-9","article-title":"Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards","volume":"39","author":"Andreani","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3000605211063695","DOI":"10.1177\/03000605211063695","article-title":"Virucidal effect of povidone-iodine against SARS-CoV-2 in vitro","volume":"49","author":"Wang","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fphar.2020.561334","article-title":"Anti-SARS-CoV natural products with the potential to inhibit SARS-CoV-2 (COVID-19)","volume":"11","author":"Verma","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.chembiol.2021.11.006","article-title":"Acriflavine, a Clinically Approved Drug, Inhibits SARS-CoV-2 and Other Betacoronaviruses","volume":"29","author":"Napolitano","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.antiviral.2017.12.015","article-title":"Disulfiram Can Inhibit MERS and SARS Coronavirus Papain-like Proteases via Different Modes","volume":"150","author":"Lin","year":"2018","journal-title":"Antiviral Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"948553","DOI":"10.3389\/fchem.2022.948553","article-title":"Structural similarities between SARS-CoV2 3CLpro and other viral proteases suggest potential lead molecules for developing broad spectrum antivirals","volume":"10","author":"Bafna","year":"2022","journal-title":"Front. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109133","DOI":"10.1016\/j.celrep.2021.109133","article-title":"Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture","volume":"35","author":"Bafna","year":"2021","journal-title":"Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e02680-20","DOI":"10.1128\/AAC.02680-20","article-title":"Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro","volume":"65","author":"Gammeltoft","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","first-page":"22425","article-title":"In search of preventive strategies: Novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues","volume":"12","author":"Wang","year":"2020","journal-title":"Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1128\/JVI.00136-06","article-title":"DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets","volume":"80","author":"Chaipan","year":"2006","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15189","DOI":"10.1128\/JVI.79.24.15189-15198.2005","article-title":"The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity","volume":"79","author":"Barretto","year":"2005","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"592289","DOI":"10.3389\/fchem.2020.592289","article-title":"Supporting SARS-CoV-2 Papain-Like Protease Drug Discovery: In silico Methods and Benchmarking","volume":"8","author":"Ibrahim","year":"2020","journal-title":"Front. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/s41590-021-00942-0","article-title":"RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells","volume":"22","author":"Yamada","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13638","DOI":"10.1038\/s41598-021-92940-3","article-title":"The RNA sensor MDA5 detects SARS-CoV-2 infection","volume":"11","author":"Sampaio","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41564-021-00884-1","article-title":"ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity","volume":"6","author":"Liu","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_73","unstructured":"Daiwa Pharmaceutical Co., Ltd (2017, October 22). BioBran Rice Bran Arabinoxylan Compound. Available online: http:\/\/www.daiwa-pharm.com\/english\/product\/biobran.html."},{"key":"ref_74","unstructured":"Tazawa, K. (2006). BioBran\/MGN-3 (Rice Bran Arabinoxylan Deritive): Basic and Clinical Application to Integrative Medicine, Iyakushuppan Co. Publishers."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1034\/j.1600-0773.2003.920608.x","article-title":"Modified rice bran beneficial for weight loss of mice as a major and acute adverse effect of cisplatin","volume":"92","author":"Endo","year":"2003","journal-title":"Pharmacol Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1300\/J133v03n04_02","article-title":"The effect of MGN-3 on cisplatin and doxorubicin induced toxicity in the rat","volume":"3","author":"Jacoby","year":"2001","journal-title":"J. Nutraceuticals Funct. Med. Foods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2376-0281","DOI":"10.4172\/2376-0281.1000205","article-title":"Improvement of quality of life in tumor patients after an immunomodulatory treatment with standardized mistletoe lectin and arabinoxylan plant extracts","volume":"3","author":"Hajto","year":"2016","journal-title":"Int. J. Neurorehabilit."},{"key":"ref_78","unstructured":"Ghoneum, M. (1999, January 11\u201313). Immunostimulation and cancer prevention. Proceedings of the 7th International Congress on Anti-aging and Biomedical Technologies, Las Vegas, NV, USA."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"NP26","DOI":"10.1177\/1534735416642287","article-title":"Chemopreventive Activity of MGN-3\/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells","volume":"15","author":"Pan","year":"2016","journal-title":"Integr. Cancer Ther."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/2\/453\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:06:36Z","timestamp":1760119596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/2\/453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,15]]},"references-count":79,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["nu15020453"],"URL":"https:\/\/doi.org\/10.3390\/nu15020453","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,15]]}}}