{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:53:09Z","timestamp":1778608389193,"version":"3.51.4"},"reference-count":36,"publisher":"IMR Press","issue":"10","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have a wide application in treating infectious and non-infectious diseases. Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum), is an important Traditional Chinese Medicine with actions of clearing away heat and eliminating dampness, draining the gallbladder to relieve jaundice, removing blood stasis to alleviate pain, resolving phlegm and arrest cough. In the search for anti-SARS-CoV-2, P. cuspidatum was recommended as as a therapeutic drug of COVID-19 pneumonia.In this study, we aimed to identifies P. cuspidatum is the potential broad-spectrum inhibitor for the treatment of coronaviruses infections. Methods: In the present study , we infected human malignant embryonal rhabdomyoma (RD) cells with the OC43 strain of the coronavirus, which represent an alternative model for SARS-CoV-2 and then employed the cell viability assay kit for the antiviral activity. We combined computer aided virtual screening to predicte the binding site and employed Surface plasmon resonance analysis (SPR) to comfirm the interaction between drugs and coronavirus. We employed fluorescence resonance energy transfer technology to identify drug\u2019s inhibition in the proteolytic activity of 3CLpro and Plpro. Results: Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly suppressed HCoV-OC43 replication. 50% inhibitory concentration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 \u03bcm, respectively. IC50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 \u03bcM, respectively. Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein. Conclusions: we identified the antiviral activity of flavonoids polydatin and resveratrol on RD cells. Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases. In summary, this study identifies P. cuspidatum as the potential broad-spectrum inhibitor for the treatment of coronaviruses infections.<\/jats:p>","DOI":"10.52586\/4988","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T07:57:21Z","timestamp":1635494241000},"source":"Crossref","is-referenced-by-count":34,"title":["Effective inhibition of coronavirus replication by Polygonum cuspidatum"],"prefix":"10.31083","volume":"26","author":[{"given":"Huan","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China"},{"name":"New Drug R&D Center, North China Pharmaceutical Corporation, 050015 Shijiazhuang, Hebei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shidong","family":"Song","sequence":"first","affiliation":[{"name":"Nanjing Gemni Biotechnology Co., Ltd, 210023 Nanjing, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Xiao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, China"},{"name":"Nanjing Gemni Biotechnology Co., Ltd, 210023 Nanjing, Jiangsu, China"},{"name":"Guangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research, 518055 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanqing","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boxuan","family":"Huang","sequence":"first","affiliation":[{"name":"Institute for Advanced Study, Shenzhen University, 518052 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengsi","family":"Sun","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqing","family":"Su","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demin","family":"Zhou","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanyu","family":"Wang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research, 518055 Shenzhen, Guangdong, China"},{"name":"Department of Biology, Southern University of Science and Technology, 518055 Shenzhen, Guangdong, China"},{"name":"Guangdong Provincial Key Laboratory of Computational Science and Material Design, 518055 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Hao","sequence":"first","affiliation":[{"name":"School of Nursing, Hebei Medical University, 050000 Shijiazhuang, Hebei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Pharmaceutical College, Hebei Medical University, 050017 Shijiazhuang, Hebei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine. 2020; 382: 727\u2013733.","DOI":"10.1056\/NEJMoa2001017"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020; 395: 497\u2013506.","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. the Lancet. 2020; 395: 565\u2013574.","DOI":"10.1016\/S0140-6736(20)30251-8"},{"key":"ref4","unstructured":"WHO. WHO\u2019s COVID-19 response. 2020. Available at: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/interactive-timeline (Accessed: 14 September 2021)."},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Fan H, Wang L, Liu W, An X, Liu Z, He X, et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model. Chinese Medical Journal. 2020; 133: 1051\u20131056.","DOI":"10.1097\/CM9.0000000000000797"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Drozdzal S, Rosik J, Lechowicz K, Machaj F, Kotfis K, Ghavami S, et al. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 2020; 53: 100719.","DOI":"10.1016\/j.drup.2020.100719"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Kang Y, Chou Y, Rothlauf PW, Liu Z, Soh TK, Cureton D, et al. Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proceedings of the National Academy of Sciences. 2020; 117: 20803\u201320813.","DOI":"10.1073\/pnas.2007837117"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Ding Y, Zeng L, Li R, Chen Q, Zhou B, Chen Q, et al. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Complementary and Alternative Medicine. 2017; 17: 130.","DOI":"10.1186\/s12906-017-1585-7"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Luo E, Zhang D, Luo H, Liu B, Zhao K, Zhao Y, et al. Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China. Chinese Medicine. 2020; 15: 34.","DOI":"10.1186\/s13020-020-00317-x"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Runfeng L, Yunlong H, Jicheng H, Weiqi P, Qinhai M, Yongxia S, et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacological Research. 2020; 156: 104761.","DOI":"10.1016\/j.phrs.2020.104761"},{"key":"ref11","unstructured":"Zhong HS. Science of Chinese materia medica. China Press of Traditional Chinese Medicine. 2016."},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Lin S, Ho C, Chuo W, Li S, Wang TT, Lin C. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infectious Diseases. 2017; 17: 144.","DOI":"10.1186\/s12879-017-2253-8"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Zhang C, Zhang X, Zhang Y, Xu Q, Xiao H, Liang X. Analysis of estrogenic compounds in Polygonum cuspidatum by bioassay and high performance liquid chromatography. Journal of Ethnopharmacology. 2006; 105: 223\u2013228.","DOI":"10.1016\/j.jep.2005.10.029"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Lin CJ, Lin HJ, Chen TH, Hsu YA, Liu CS, Hwang GY, et al. Polygonum cuspidatum and its active components inhibit replication of the influenza virus through toll-like receptor 9-induced interferon beta expression. PLos ONE. 2015; 10: e0117602.","DOI":"10.1371\/journal.pone.0117602"},{"key":"ref15","unstructured":"Chinese scientists discover old drugs and herbal medicines that may work against novel coronaviruses, including montelukast, Polygonum cuspidatum, Cinanserin. 2020. Available at: https:\/\/www.medsci.cn\/article\/show_article.do?ac=good&action=view_do&id=1535186e30d7 (Accessed: 14 September 2021)."},{"key":"ref16","unstructured":"Zhang Boli on Tranditional Chinese medicine against epidemics: Polygonum cuspidatum and verbena inhibite COVID-19. 2020. Available at: https:\/\/finance.sina.com.cn\/chanjing\/cyxw\/2020-04-03\/doc-iimxyqwa4826348.shtml (Accessed: 14 September 2021)."},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Wu F, Zhao S, Yu B, Chen Y, Wang W, Song Z, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579: 265\u2013269.","DOI":"10.1038\/s41586-020-2008-3"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host & Microbe. 2020; 27: 325\u2013328.","DOI":"10.1016\/j.chom.2020.02.001"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Klemm T, Ebert G, Calleja DJ, Allison CC, Richardson LW, Bernardini JP, et al. Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2. The EMBO Journal. 2020; 39: e106275.","DOI":"10.15252\/embj.2020106275"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Zhang LL, Lin DZ, Sun XYY, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors. Science. 2020; 368: 409\u2013412.","DOI":"10.1126\/science.abb3405"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Liu Y, Liang C, Xin L, Ren X, Tian L, Ju X, et al. The development of Coronavirus 3C-Like protease (3CLpro) inhibitors from 2010 to 2020. European Journal of Medicinal Chemistry. 2020; 206: 112711.","DOI":"10.1016\/j.ejmech.2020.112711"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Rathnayake AD, Zheng J, Kim Y, Perera KD, Mackin S, Meyerholz DK, et al. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV\u2013infected mice. Science Translational Medicine. 2020; 12: eabc5332.","DOI":"10.1126\/scitranslmed.abc5332"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Kim DE, Min JS, Jang MS, Lee JY, Shin YS, Song JH, et al. Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells. Biomolecules. 2019; 9: 696.","DOI":"10.3390\/biom9110696"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Xu H, Liu B, Xiao Z, Zhou M, Ge L, Jia F, et al. Computational and Experimental Studies Reveal that Thymoquinone Blocks the Entry of Coronaviruses into in Vitro Cells. Infectious Diseases and Therapy. 2021; 10: 483\u2013494.","DOI":"10.1007\/s40121-021-00400-2"},{"key":"ref25","unstructured":"Douglas M.B, Donald G.W. Nonlinear Regression Analysis and Its Applications. John Wiley and Sons: Hoboken. 1988."},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry. 2010; 31: 455\u2013461.","DOI":"10.1002\/jcc.21334"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Tang Y, Zeng X, Liang J. Surface Plasmon Resonance: an Introduction to a Surface Spectroscopy Technique. Journal of Chemical Education. 2010; 87: 742\u2013746.","DOI":"10.1021\/ed100186y"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Brown AS, Ackerley DF, Calcott MJ. High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor. Molecules. 2020; 25: 4666.","DOI":"10.3390\/molecules25204666"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Xian Y, Zhang J, Bian Z, Zhou H, Zhang Z, Lin Z, et al. Bioactive natural compounds against human coronaviruses: a review and perspective. Acta Pharmaceutica Sinica B. 2020; 10: 1163\u20131174.","DOI":"10.1016\/j.apsb.2020.06.002"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Ma QH, Pan WQ, Li RF, Liu B, Li CF, Xie YQ, et al. Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-kappa B signaling pathway. Pharmacological Research. 2020; 158: 104850.","DOI":"10.1016\/j.phrs.2020.104850"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Huang Y, Bai C, He F, Xie Y, Zhou H. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19). Pharmacological Research. 2020; 158: 104939.","DOI":"10.1016\/j.phrs.2020.104939"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Lu A. Theory of traditional Chinese medicine and therapeutic method of diseases. World Journal of Gastroenterology. 2004; 10: 1854.","DOI":"10.3748\/wjg.v10.i13.1854"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Cho JK, Curtis-Long MJ, Lee KH, Kim DW, Ryu HW, Yuk HJ, et al. Geranylated flavonoids displaying SARS-CoV papain-like protease inhibition from the fruits of Paulownia tomentosa. Bioorganic & Medicinal Chemistry. 2013; 21: 3051\u20133057.","DOI":"10.1016\/j.bmc.2013.03.027"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Jo S, Kim S, Shin DH, Kim M. Inhibition of SARS-CoV 3CL protease by flavonoids. Journal of Enzyme Inhibition and Medicinal Chemistry. 2020; 35: 145\u2013151.","DOI":"10.1080\/14756366.2019.1690480"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Daczkowski CM, Dzimianski JV, Clasman JR, Goodwin O, Mesecar AD, Pegan SD. Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. Journal of Molecular Biology. 2017; 429: 1661\u20131683.","DOI":"10.1016\/j.jmb.2017.04.011"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Hsu M, Kuo C, Chang K, Chang H, Chou C, Ko T, et al. Mechanism of the Maturation Process of SARS-CoV 3CL Protease. Journal of Biological Chemistry. 2005; 280: 31257\u201331266. .","DOI":"10.1074\/jbc.M502577200"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/26\/10\/10.52586\/4988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:21:43Z","timestamp":1732706503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/26\/10\/10.52586\/4988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,30]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021]]}},"alternative-id":["s2768-6701(21)00043-5"],"URL":"https:\/\/doi.org\/10.52586\/4988","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,30]]},"article-number":"789"}}