Effective inhibition of coronavirus replication by Polygonum cuspidatum
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 m...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2021-10-01
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| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/26/10/10.52586/4988 |
| _version_ | 1819023021451509760 |
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| author | Huan Xu Jing Li Shidong Song Zhen Xiao Xuanqing Chen Boxuan Huang Mengsi Sun Guoqing Su Demin Zhou Guanyu Wang Ran Hao Na Wang |
| author_facet | Huan Xu Jing Li Shidong Song Zhen Xiao Xuanqing Chen Boxuan Huang Mengsi Sun Guoqing Su Demin Zhou Guanyu Wang Ran Hao Na Wang |
| author_sort | Huan Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T04:32:16Z |
| format | Article |
| id | doaj.art-93d28ba0fdc74eaf92f5e6ada9bf35fe |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-12-21T04:32:16Z |
| publishDate | 2021-10-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-93d28ba0fdc74eaf92f5e6ada9bf35fe2022-12-21T19:15:54ZengIMR PressFrontiers in Bioscience-Landmark2768-67012021-10-01261078979810.52586/4988s2768-6701(21)00043-5Effective inhibition of coronavirus replication by Polygonum cuspidatumHuan Xu0Jing Li1Shidong Song2Zhen Xiao3Xuanqing Chen4Boxuan Huang5Mengsi Sun6Guoqing Su7Demin Zhou8Guanyu Wang9Ran Hao10Na Wang11Institute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, ChinaNanjing Gemni Biotechnology Co., Ltd, 210023 Nanjing, Jiangsu, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, 430000 Wuhan, Hubei, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191 Beijing, ChinaInstitute for Advanced Study, Shenzhen University, 518052 Shenzhen, Guangdong, ChinaInstitute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, ChinaInstitute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, ChinaInstitute of Chemical Biology, Shenzhen Bay Laboratories, 518132 Shenzhen, Guangdong, ChinaGuangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research, 518055 Shenzhen, Guangdong, ChinaSchool of Nursing, Hebei Medical University, 050000 Shijiazhuang, Hebei, ChinaDepartment of Pharmacognosy, Pharmaceutical College, Hebei Medical University, 050017 Shijiazhuang, Hebei, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/26/10/10.52586/4988polydatinresveratrolcoronavirussars-cov-2oc43-covmain proteasepapain-like proteasebroad-spectrump. cuspidatum |
| spellingShingle | Huan Xu Jing Li Shidong Song Zhen Xiao Xuanqing Chen Boxuan Huang Mengsi Sun Guoqing Su Demin Zhou Guanyu Wang Ran Hao Na Wang Effective inhibition of coronavirus replication by Polygonum cuspidatum Frontiers in Bioscience-Landmark polydatin resveratrol coronavirus sars-cov-2 oc43-cov main protease papain-like protease broad-spectrum p. cuspidatum |
| title | Effective inhibition of coronavirus replication by Polygonum cuspidatum |
| title_full | Effective inhibition of coronavirus replication by Polygonum cuspidatum |
| title_fullStr | Effective inhibition of coronavirus replication by Polygonum cuspidatum |
| title_full_unstemmed | Effective inhibition of coronavirus replication by Polygonum cuspidatum |
| title_short | Effective inhibition of coronavirus replication by Polygonum cuspidatum |
| title_sort | effective inhibition of coronavirus replication by polygonum cuspidatum |
| topic | polydatin resveratrol coronavirus sars-cov-2 oc43-cov main protease papain-like protease broad-spectrum p. cuspidatum |
| url | https://www.imrpress.com/journal/FBL/26/10/10.52586/4988 |
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