Effective inhibition of coronavirus replication by Polygonum cuspidatum.

Boxuan Huang ,Meng-Si Sun ,Xuan-Qing Chen ,Shidong Song ,Guanyu Wang ,Na Wang ,Zhen Xiao ,Guo-Qing Su ,Ran Hao ,Demin Zhou ,Huan Xu ,Jing Li

doi:10.52586/4988

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.

Highlights

An unusual pneumonia of unknown origin was reported in December 2019 [1]
While searching for a severe acute respiratory virus (SARS)-CoV-2 3CLpro and PLpro inhibitor from natural sources, we found that polydatin and resveratrol from P. cuspidatum possessed inhibitory activity against both the proteases
To verify the inhibitory effect of polydatin and resveratrol on coronavirus at the cellular level in vitro, we measured the antiviral activity of polydatin and resveratrol by indirect immunofluorescence assay (IFA) on RD cells infected with OC43-CoV which is an alternative model for SARS-CoV-2

Summary

Introduction

Its clinical features are similar to those of severe acute respiratory virus (SARS) [2]. The viral genome isolated from patients clustered into a clade of betacoronaviruses was distinct from that of the severe acute respiratory syndrome coronavirus (SARS-CoV) [3]. This disease, named the coronavirus disease 2019 (COVID-19) was caused by a novel coronavirus (2019nCoV), which was later renamed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2020, several vaccines shown to be highly effective were granted emergency use authorization. While vaccines will prevent disease occurrence, infected individuals still need treatment options, and repurposing drugs circumvents the lengthy and costly process of drug development. It is urgent to excavate the efficacy of currently approved drugs for the treatment of COVID-19 [5,6,7]

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