Geraniin as a potential inhibitor of SARS-CoV-2 3CL<sup>pro</sup>

Yu, Wendi; Jin, Qiying; Zeng, Mao-Sen; Liu, Jinyuan; Xu, Pao

doi:10.1080/14786419.2022.2043308

Cited by 5 publications

References 20 publications

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Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Zhang

Yan

Zhou

et al. 2023

Natural Product Research

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Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary.Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that geraniin is not a potential inhibitor against Mpro based on the results from a set of in vitro assays. These results suggest a stringent in vitro validation with diverse biochemical assays is essential for the discovery of Mpro inhibitors, and the fluorescence quenching effect caused by natural products should be considered when evaluating Mpro inhibitors.

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Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Zhang

Yan

Zhou

et al. 2023

Natural Product Research

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Geraniin Alleviates Mouse Laser‐Induced Choroidal Neovascularisation by Inhibiting Choroidal Endothelial Cell ACE2/Ang‐(1–7)/MasR/IL‐10 Pathway

Lu,

Cai,

et al. 2024

J Cellular Molecular Medi

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Anti‐vascular endothelial growth factor (VEGF) drugs suppress choroidal neovascularisation (CNV), thus improving vision. However, some patients may have a poor response or develop resistance to anti‐VEGF drugs. Geraniin (GE), a polyphenol isolated from an herb called Phyllanthus amarus, possesses anti‐angiogenic properties. This study aimed to explore the mechanism of action of GE in CNV. GE was found to activate the angiotensin‐converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang‐[1–7])/MAS1 proto‐oncogene, G protein‐coupled receptor (MasR)/interleukin‐10 (IL‐10) pathway in hypoxic human choroidal endothelial cells (HCECs) in vitro and mouse models of laser‐induced CNV in vivo. Activation of the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway by GE attenuated the proliferative, migratory, and tube‐forming abilities of hypoxic HCECs and prevented the development of CNV in mice. Notably, GE did not cause ocular or systemic toxicity in mice with CNV. These findings suggest that GE alleviates CNV by activating the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway in choroidal endothelial cells (CECs).

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Discovery of novel SARS-CoV-2 3CLpro inhibitors from natural products by FRET-based assay

Zhang,

Ye,

Wang

et al. 2024

Preprint

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As a highly conserved protease, 3-chymotrypsin-like protease (3CLpro) plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, and drugs targeting 3CLpro have shown promising therapeutic effects. Promising applications have been achieved with direct-acting antivirals targeting 3CLpro. Natural products are an important source of medicinal compounds. In this study, we expressed and purified fusion proteins and obtained soluble 3CLpro, and the enzymatic activity was evaluated using fluorescence resonance energy transfer (FRET) assays at optimized concentrations of protease and substrate. This assay was further applied to validate the 3CLpro inhibitory activity of 30 compounds selected from 583 compounds via virtual screening. Epitheaflagallin 3-O-gallate (ETFGg) was identified with binding free energy of − 66.90 kcal/mol and an IC50 value of 8.73 ± 2.30 µM and was selected for the ligand-protein interaction study. Dynamics simulation results suggested that ETFGg interacted with HIE163, THR190 and GLN192 of 3CLpro, and was stable in the binding pocket of 3CLpro during the simulation. Together, this work identified ETFGg as a 3CLpro inhibitor with prominent binding capability, which could serve as a potential lead compound for drug development against COVID-19.

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Geraniin as a potential inhibitor of SARS-CoV-2 3CL^pro

Cited by 5 publications

References 20 publications

Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Geraniin Alleviates Mouse Laser‐Induced Choroidal Neovascularisation by Inhibiting Choroidal Endothelial Cell ACE2/Ang‐(1–7)/MasR/IL‐10 Pathway

Discovery of novel SARS-CoV-2 3CLpro inhibitors from natural products by FRET-based assay

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Geraniin as a potential inhibitor of SARS-CoV-2 3CLpro

Cited by 5 publications

References 20 publications

Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Geraniin Alleviates Mouse Laser‐Induced Choroidal Neovascularisation by Inhibiting Choroidal Endothelial Cell ACE2/Ang‐(1–7)/MasR/IL‐10 Pathway

Discovery of novel SARS-CoV-2 3CLpro inhibitors from natural products by FRET-based assay

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Geraniin as a potential inhibitor of SARS-CoV-2 3CL^pro