Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Liu, Jiazheng; Meng, Jie-Ru; Li, Runfeng; Jiang, Haiming; Fu, Lu; Xu, Ting; Zhu, Guo‐Yuan; Zhang, Wei; Gao, Jin; Jiang, Zhihong; Yang, Zifeng; Bai, Liping

doi:10.3389/fpls.2022.988655

Cited by 10 publications

(9 citation statements)

References 54 publications

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“…Thirty-one flavonoids ( Figure 1 ) were firstly evaluated for their inhibitory activity against SARS-CoV-2 entry into host cells using a well-established SARS-CoV-2 pseudovirus assay [ 35 , 36 , 37 , 38 ]. Cepharanthine, a reported inhibitor of viral entry, was used as a positive control [ 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…SARS-CoV-2 pseudovirus was prepared by the same approach as previously published [ 35 , 36 , 37 , 38 ]. The spike protein expression plasmid (pcDNA3.1-SARS-CoV-2-Spike-Myc) was co-transfected with the HIV backbone vector pNL4-3.Luc.R-E- into HEK-293T cells by the Lipo8000 transfection reagent.…”

Section: Methodsmentioning

confidence: 99%

“…The epigallocatechin-3-gallate (EGCG) was also reported to significantly inhibit SARS-CoV-2 and other coronavirus infections by blocking the spike–ACE2 interaction [ 34 ]. Similarly, our group have found that baicalein and scutellarein (bioactive flavonoids of Scutellariae Radix ) inhibited viral entry by targeting the interaction of viral spike with ACE2 receptor [ 35 ]. All the above findings suggested that different subclasses of flavonoids have the potential as SARS-CoV-2 entry inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD

Meng

Liu

et al. 2023

Viruses

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COVID-19 is still a global public health concern, and the SARS-CoV-2 mutations require more effective antiviral agents. In this study, the antiviral entry activity of thirty-one flavonoids was systematically evaluated by a SARS-CoV-2 pseudovirus model. Twenty-four flavonoids exhibited antiviral entry activity with IC50 values ranging from 10.27 to 172.63 µM and SI values ranging from 2.33 to 48.69. The structure–activity relationship of these flavonoids as SARS-CoV-2 entry inhibitors was comprehensively summarized. A subsequent biolayer interferometry assay indicated that flavonoids bind to viral spike RBD to block viral interaction with ACE2 receptor, and a molecular docking study also revealed that flavonols could bind to Pocket 3, the non-mutant regions of SARS-CoV-2 variants, suggesting that flavonols might be also active against virus variants. These natural flavonoids showed very low cytotoxic effects on human normal cell lines. Our findings suggested that natural flavonoids might be potential antiviral entry agents against SARS-CoV-2 via inactivating the viral spike. It is hoped that our study will provide some encouraging evidence for the use of natural flavonoids as disinfectants to prevent viral infections.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD

Meng

Liu

et al. 2023

Viruses

Self Cite

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“…In previous studies, the pseudovirus of SARS-CoV-2 combined various protease inhibitor treatments to demonstrate that both cell membrane fusion and the endocytosis pathway would exist in the SARS-CoV-2 entry [23]. A pseudovirus system, containing the SARS-CoV-2 spike protein and the Firefly luciferase reporter gene, was used to investigate the ability of traditional medicine ingredients to inhibit viral entry [28,29]. On the other hand, SARS-CoV-2 spike-expressing cells were used to mimic the interaction of spike and host facts and the cytopathic effects of SARS-CoV-2 infection [30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2

Chang

Chu

Chen

et al. 2022

Viruses

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Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development. In this study, to generate SARS-CoV-2 VLPs (SCoV2-SEM VLPs) composed of three structural proteins including spike (S), envelop (E) protein and membrane (M) protein, a tri-cistronic vector expression system was established in a cell line co-expressing SARS-CoV-2 S, E and M proteins. The SCoV2-SEM VLPs were harvested from the cultured medium, and three structure proteins were confirmed by Western blot assay. A negative-stain TEM assay demonstrated the size of the SCoV2-SEM VLPs with a diameter of about 90 nm. To further characterize the infectious properties of SCoV2-SEM VLPs, the VLPs (atto647N-SCoV2-SEM VLPs) were fluorescence-labeled by conjugation with atto-647N and visualized under confocal microscopy at a single-particle resolution. The results of the infection assay revealed that atto647N-SCoV2-SEM VLPs attached to the surface of the HEK293T cells at the pre-binding phase in a ACE2-dependent manner. At the post-infection phase, atto647N-SCoV2-SEM VLPs either fused with the cellular membrane or internalized into the cytoplasm with mCherry-rab5-positive early endosomes. Moreover, fusion with the cellular membrane and the internalization with early endosomes could be inhibited by the treatment of camostat (a pharmacological inhibitor of TMPRSS2) and chlorpromazine (an endocytosis inhibitor), respectively. These results elucidated that SCoV2-SEM VLPs behave similarly to the authentic live SARS-CoV-2 virus, suggesting that the development of SCoV2-SEM VLPs provide a realistic and safe experimental model for studying the infectious mechanism of SARS-CoV-2.

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“…Huangqin is considered to be an "herbal antibiotic" that can fight against COVID-19. Based on a network analysis, Huangqin primarily regulated the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin and blocked SARS-CoV-2 spike binding to human ACE2 receptors (20). In addition, in vitro bioassays showed that Baicalein inhibited SARS-CoV-2 from entering into Vero E6 cells.…”

Section: Single Herbsmentioning

confidence: 99%

Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19

Zhang

2023

BST

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as well as the release of new viral particles. Therefore, ACE2 should be a target to screen drugs inhibiting the replication and proliferation of SARS-COV-2.Recently, many herbal medicines have exhibited a high affinity for ACE2 in treating COVID-19 (3). These herbal medicines can target ACE2 to prevent SARS-CoV-2 from entering into host cells. The current work has summarized these herbal medicines including formulas, single herbs, and active ingredients, which have exhibited a high affinity for ACE2 in treating COVID-19 (Figure 1). This work may provide meaningful and useful information on further research to investigate the mechanisms of herbal medicines against SARS-CoV-2. Herbal formulasCOVID-19 is categorized as a pestilence according to traditional Chinese medicine (TCM) theory. Herbal medicines have been used to treat and prevent viral infections for thousands of years, and herbalists have

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Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Abstract: Yang Z-F and Bai L-P (2022) Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19.

Cited by 10 publications

References 54 publications

Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD

Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD

Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2

Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19

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