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Effective inhibition of coronavirus replication by Polygonum cuspidatum.
Xu, Huan; Li, Jing; Song, Shidong; Xiao, Zhen; Chen, Xuanqing; Huang, Boxuan; Sun, Mengsi; Su, Guoqing; Zhou, Demin; Wang, Guanyu; Hao, Ran; Wang, Na.
  • Xu H; Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China.
  • Li J; New Drug R&D Center, North China Pharmaceutical Corporation, 050015 Shijiazhuang, Hebei, China.
  • Song S; School of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, China.
  • Xiao Z; Nanjing Gemni Biotechnology Co., Ltd, 210023 Nanjing, Jiangsu, China.
  • Chen X; School of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, China.
  • Huang B; Nanjing Gemni Biotechnology Co., Ltd, 210023 Nanjing, Jiangsu, China.
  • Sun M; Guangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research, 518055 Shenzhen, Guangdong, China.
  • Su G; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191 Beijing, China.
  • Zhou D; Institute for Advanced Study, Shenzhen University, 518052 Shenzhen, Guangdong, China.
  • Wang G; Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China.
  • Hao R; Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China.
  • Wang N; Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, China.
Front Biosci (Landmark Ed) ; 26(10): 789-798, 2021 10 30.
Article in English | MEDLINE | ID: covidwho-1498508
ABSTRACT

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's 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 µm, 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 µM, 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.
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Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stilbenes / Virus Replication / Drugs, Chinese Herbal / Fallopia japonica / Resveratrol / SARS-CoV-2 / Glucosides Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Front Biosci (Landmark Ed) Year: 2021 Document Type: Article Affiliation country: 4988

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stilbenes / Virus Replication / Drugs, Chinese Herbal / Fallopia japonica / Resveratrol / SARS-CoV-2 / Glucosides Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Front Biosci (Landmark Ed) Year: 2021 Document Type: Article Affiliation country: 4988