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Identification of the potential TLR7 antagonists by virtual screening and experimental validation

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Abstract

Toll-like receptor 7 (TLR7) is highly expressed in dendritic cells (DCs) and B cells, and its aberrant activation can promote disease progression in systemic lupus erythematosus (SLE). We utilized structure-based virtual screening and experimental validation to screen natural products from TargetMol for potential TLR7 antagonists. Our results of molecular docking and molecular dynamics simulation showed that Mogroside V (MV) strongly interacted with TLR7, with stable open-TLR7-MV and close-TLR7-MV complexes. Furthermore, in vitro experiments demonstrated that MV significantly inhibited B cell differentiation in a concentration-dependent manner. In addition to TLR7, we also revealed a strong interaction of MV with all TLRs, including TLR4. The above results suggested that MV might be a potential TLR7 antagonist deserving of further study.

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Data availability

The all datasets are available from the corresponding author.

Abbreviations

TLR7:

Toll-like receptor 7

SLE:

Systemic lupus erythematosus

HCQ:

Hydroxychloroquine

MD:

Molecular dynamic simulation

PCA:

Principal component analysis

RMSD:

The root-mean-square deviations

RMSF:

The root-mean-square fluctuation

SASA:

The solvent-accessible surface area

FELs:

Free energy landscapes

PBMCs:

Peripheral blood mononuclear cells

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Acknowledgements

This work was supported by the China Postdoctoral Science Foundation (2022M723563) and Natural Science Foundation of Hunan Province (2022JJ40722).

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Authors and Affiliations

  1. Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China

    Pinglang Ruan, Miao Yang & Ming Yang

  2. Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Susu Wang

  3. Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

    Ping Yi

  4. Department of Dermatology, Hunan Provincial People’s Hospital, Changsha, 410078, Hunan, China

    Yongjian Chen

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  1. Pinglang Ruan
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  2. Susu Wang
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  4. Miao Yang
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Contributions

PL R wrote the manuscript; YJ C, M Y and SS W did the editing; M Y designed and revised the manuscript.

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Correspondence to Ming Yang.

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Ruan, P., Wang, S., Yi, P. et al. Identification of the potential TLR7 antagonists by virtual screening and experimental validation. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10660-4

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