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. 2022 Nov 14;29(3):205–212. doi: 10.1007/s11655-022-3686-5

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants

Zhen Xiao 1,2, Huan Xu 3, Ze-yang Qu 1,2, Xin-yuan Ma 4, Bo-xuan Huang 2,5, Meng-si Sun 3, Bu-qing Wang 6, Guan-yu Wang 1,2,7,8,✉
PMCID: PMC9661462  PMID: 36374439

Abstract

Objective

To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin.

Methods

A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43.

Results

The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43.

Conclusions

The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Electronic Supplementary Material

Supplementary material (Appendix 1) is available in the online version of this article at 10.1007/s11655-022-3686-5.

Keywords: Reduning injection, Chinese medicine, luteolin, quercetin, SARS-CoV-2

Supplementary material to

11655_2022_3686_MOESM1_ESM.pdf (677.7KB, pdf)

Active Ingredients of Reduning Injections Maintain High Potency against SARS-CoV-2 Variants

Acknowledgement

We thank Bioimaging Core and Biochemical Analysis Platform of Shenzhen Bay Laboratory for providing imaging and SPR support. We also would like to acknowledge Bioimaging Core engineer HUANG Shi-xian for assistance with fluorescence microscope.

Author Contributions

Xu H, Wang GY acquired funding and supervised the project. Xiao Z, Xu H, Sun MS performed the experiments. Xu H, Wang GY and Xiao Z were responsible for writing and revising the article. Qu ZY did the virtual screening. Ma XY, Huang BX and Wang BQ analyzed the data. Xiao Z, Xu H and Qu ZY contributed to this work equally. All the authors read and approved the final version of manuscript.

Conflict of Interest

The authors declare no conflicts of interest.

Footnotes

Supported by National Key R&D Plan Project (No. 2019YFA0906002), National Natural Science Foundation of China (No. 32070681)

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Supplementary Materials

11655_2022_3686_MOESM1_ESM.pdf (677.7KB, pdf)

Active Ingredients of Reduning Injections Maintain High Potency against SARS-CoV-2 Variants

Articles from Chinese Journal of Integrative Medicine are provided here courtesy of Nature Publishing Group

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