4.5 Article

Effective inhibition of coronavirus replication by Polygonum cuspidatum

Journal

FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 26, Issue 10, Pages 789-798

Publisher

IMR PRESS
DOI: 10.52586/4988

Keywords

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

Funding

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

Ask authors/readers for more resources

During the pandemic, traditional Chinese medicine P. cuspidatum is considered as a potential broad-spectrum inhibitor for the treatment of coronavirus infections, with the ability to suppress virus replication and serve as specific and selective inhibitors for SARS-CoV-2 and viral cysteine proteases like 3CLpro and PLpro.
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.

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