A Biolayer Interferometry‐Based SARS‐COV‐2 Mpro‐Targeted Active Ingredients Recognition System: Construction and Application in Ligand Screening From Herbal Medicines

Dai Zhang; Bing Han; Xiao‐Fei Chen; Shuai Zhao; Wei‐Xia Li; Ming‐Liang Zhang; Meng‐Qi Huo; Yong‐Sheng Qiu; Ying‐Jie Ren; Yao‐Dong Zhang; Xian‐Qing Ren; Wei Wang; Jin‐Fa Tang

doi:10.1002/pca.3462

journal article Nov 20, 2024

A Biolayer Interferometry‐Based SARS‐COV‐2 Mpro‐Targeted Active Ingredients Recognition System: Construction and Application in Ligand Screening From Herbal Medicines

Dai Zhang

Bing Han

Xiao‐Fei Chen Shuai Zhao

Wei‐Xia Li Ming‐Liang Zhang Meng‐Qi Huo Yong‐Sheng Qiu Ying‐Jie Ren Yao‐Dong Zhang Xian‐Qing Ren Wei Wang

Jin‐Fa Tang

Phytochemical Analysis Vol. 36 No. 3 pp. 718-731 · Wiley

View at Publisher Save 10.1002/pca.3462

Abstract

ABSTRACTIntroductionDrug discovery research targeting SARS‐CoV‐2 and other emerging pathogens remains critically important. Active compounds derived from plants frequently serve as lead compounds for further drug discovery; however, numerous unrelated chemical constituents in crude extracts may obscure the effective ingredients in LC‐MS analysis.ObjectiveThe aim of this study is to construct a biolayer interferometry (BLI)‐based system for recognizing active ingredients that inhibit the main protease (Mpro) of SARS‐CoV‐2 and to identify the active chemical components binding to Mpro from herbal medicines.MethodologyWe developed a novel FRET fluorogenic probe by linking the amino acid sequences of the fluorescent proteins Lssmorange and mKate2 (Ls‐mK). The interaction between traditional Chinese medicine and Mpro was analyzed using BLI. Ultrahigh performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF‐MS) was employed to analyze the composition of herbal medicines.ResultsFluorescence detection and spectroscopy confirmed the successful construction of an Mpro inhibitor screening system. Lanqin Oral Liquid (LQL) and Gardeniae fructus exhibited strong inhibitory effects on Mpro. Ten compounds were identified from G. fructus extracts; among them, deacetyl asperulosidic acid methyl ester (DAAME) and Gardoside were found to strongly bind to Mpro, with dissociation constants (KD) of 3.41 μM and 801 nM, respectively. The half‐maximal inhibitory concentrations (IC50) of DAAME and Gardoside for Mpro were 27.46 and 13.7 μM, respectively.ConclusionThis study established a functional Mpro inhibitor screening system. Among the 10 components identified from G. fructus that bind to Mpro, DAAME and Gardoside displayed strong binding and inhibitory activity, indicating their potential as lead compounds for inhibiting SARS‐CoV‐2 viral replication.

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Details

Published: Nov 20, 2024
Vol/Issue: 36(3)
Pages: 718-731
License: View

Authors

D

Dai Zhang

Department of Laboratory Medicine First Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou China

B

Bing Han

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China

X

Xiao‐Fei Chen

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China

S

Shuai Zhao

Henan Provincial Key Laboratory of Pediatric Genes and Metabolic Diseases Zhengzhou University Affiliated Children's Hospital Zhengzhou China

W

Wei‐Xia Li

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China; Department of Pharmacy First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China

M

Ming‐Liang Zhang

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China

M

Meng‐Qi Huo

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China

Y

Yong‐Sheng Qiu

Department of Anesthesiology Zhengzhou University Affiliated Children's Hospital Zhengzhou China

Y

Ying‐Jie Ren

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China

Y

Yao‐Dong Zhang

Henan Provincial Key Laboratory of Pediatric Genes and Metabolic Diseases Zhengzhou University Affiliated Children's Hospital Zhengzhou China

X

Xian‐Qing Ren

Department of Pediatrics Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China

W

Wei Wang

Department of Infection First Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou China

J

Jin‐Fa Tang

First Affiliated Hospital Henan Provincial Center for Clinical Application, Evaluation, and Transformation of Traditional Chinese Medicine Henan Provincial Center for Safety Evaluation and Risk Control of Traditional Chinese Medicine Henan Provincial Key Laboratory of Traditional Chinese Medicine Clinical Pharmacy Henan University of Traditional Chinese Medicine Zhengzhou China; Department of Pharmacy First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China

Cite This Article

Dai Zhang, Bing Han, Xiao‐Fei Chen, et al. (2024). A Biolayer Interferometry‐Based SARS‐COV‐2 Mpro‐Targeted Active Ingredients Recognition System: Construction and Application in Ligand Screening From Herbal Medicines. Phytochemical Analysis, 36(3), 718-731. https://doi.org/10.1002/pca.3462

A Biolayer Interferometry‐Based SARS‐COV‐2 Mpro‐Targeted Active Ingredients Recognition System: Construction and Application in Ligand Screening From Herbal Medicines

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