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

Pinglang Ruan; Susu Wang; Ping Yi; Miao Yang; Yongjian Chen; Ming Yang

doi:10.1007/s11030-023-10660-4

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

Mol Divers. 2023 May 23. doi: 10.1007/s11030-023-10660-4. Online ahead of print.

Authors

Pinglang Ruan¹, Susu Wang², Ping Yi³, Miao Yang¹, Yongjian Chen⁴, Ming Yang⁵

Affiliations

¹ Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
² Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Dermatology, Hunan Provincial People's Hospital, Changsha, 410078, Hunan, China.
⁵ Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China. yangming_0216@csu.edu.cn.

PMID: 37217769
DOI: 10.1007/s11030-023-10660-4

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.

Keywords: Mogroside V; Molecular docking; Molecular dynamics simulation; Systemic lupus erythematosus; TLR7 antagonists.

Abstract

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