Effective inhibition of coronavirus replication by Polygonum cuspidatum

Xu, Huan1,2; Li, Jing3; Song, Shidong4; Xiao, Zhen3,4,5; Chen, Xuanqing6; Huang, Boxuan7; Sun, Mengsi1; Su, Guoqing1; Zhou, Demin1,6; Wang, Guanyu5,8,9; Hao, Ran10; Wang, Na11

2021-10-30

10.52586/4988

FRONTIERS IN BIOSCIENCE-LANDMARK   影响因子和分区

2768-6701

2768-6698

Background: The coronavirus disease 2019 pan-demic, 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 prod-ucts 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 eliminat- ing 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 identi- fies 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 coro- navirus, 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 vir- tual 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 iden- tify drug's inhibition in the proteolytic activity of 3CLpro and Plpro. Results: Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly sup- pressed HCoV-OC43 replication. 50% inhibitory concen- tration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 mu m, 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 mu M, respectively. Finally, SPR assay confirmed that polydatin and resver- atrol had high affinity to SARS-CoV-2, SARS-CoV 3Cl- pro, 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 infec- tions.

Polydatin Resveratrol Coronavirus SARS-CoV-2 OC43-CoV Main protease Papain-like protease Broad-spectrum P cuspidatum

SCI

英语

通讯

National Science and Technology Major project[2017ZX09303008] ; Shenzhen Bay laboratory start up fund[21230071] ; Guangdong Provincial Special Projects on COVID-19[2020KZDZX1182] ; Natural Science Foundation of China[61773196,32070681] ; Guangdong Provincial Key Laboratory of Computational Science and Material Design[2019B030301001] ; Guang-dong Provincial Key Laboratory of Cell Microenvironment and Disease Research[2017B030301018] ; Shenzhen Peacock Plan[KQTD2016053117035204] ; Hebei Natural Science Foundation["H2017206281","H2020206483"] ; Medical Science Research Project of Hebei Province[20211109]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000717677200002

BIOSCIENCE RESEARCH INST-BRI

Web of Science

1.Shenzhen Bay Labs, Inst Chem Biol, Shenzhen 518132, Guangdong, Peoples R China
2.North China Pharmaceut Corp, New Drug R&D Ctr, Shijiazhuang 050015, Hebei, Peoples R China
3.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430000, Hubei, Peoples R China
4.Nanjing Gemni Biotechnol Co Ltd, Nanjing 210023, Jiangsu, Peoples R China
5.Guangdong Prov Key Lab Cell Microenviroment & Dis, Shenzhen 518055, Guangdong, Peoples R China
6.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
7.Shenzhen Univ, Inst Adv Study, Shenzhen 518052, Guangdong, Peoples R China
8.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China
9.Guangdong Prov Key Lab Computat Sci & Mat Design, Shenzhen 518055, Guangdong, Peoples R China
10.Hebei Med Univ, Sch Nursing, Shijiazhuang 050000, Hebei, Peoples R China
11.Hebei Med Univ, Pharmaceut Coll, Dept Pharmacognosy, Shijiazhuang 050017, Hebei, Peoples R China

Xu, Huan,Li, Jing,Song, Shidong,et al. Effective inhibition of coronavirus replication by Polygonum cuspidatum[J]. FRONTIERS IN BIOSCIENCE-LANDMARK,2021,26(10).

Xu, Huan.,Li, Jing.,Song, Shidong.,Xiao, Zhen.,Chen, Xuanqing.,...&Wang, Na.(2021).Effective inhibition of coronavirus replication by Polygonum cuspidatum.FRONTIERS IN BIOSCIENCE-LANDMARK,26(10).

Xu, Huan,et al."Effective inhibition of coronavirus replication by Polygonum cuspidatum".FRONTIERS IN BIOSCIENCE-LANDMARK 26.10(2021).