Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro.

ABSTRACT: COVID-19 has become a global pandemic and there is an urgent call for developing drugs against the virus (SARS-CoV-2). The 3C-like protease (3CL^pro) of SARS-CoV-2 is a preferred target for broad spectrum anti-coronavirus drug discovery. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CL^pro activity in vitro with IC₅₀'s of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC₅₀'s of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CL^pro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CL^pro, demonstrating their potential as broad-spectrum anti-coronavirus drugs.

SUBMITTER: Liu H

PROVIDER: S-EPMC7850424 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease.

Project description: Not available

| S-EPMC8164054 | biostudies-literature

Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis Inhibit the Neuraminidase Activity of Pandemic 2009 H1N1 and Seasonal Influenza A Viruses.

Project description:This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC50 values ranging from 73.16 to 487.40??g/mL and plaque reduction IC50 values ranging from 23.7 to 27.4??g/mL. Chloroform extract showed antiviral activities with plaque reduction IC50 values ranging from 14.16 to 41.49??g/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC50?=?0.018??M) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection.

| S-EPMC3705751 | biostudies-literature

Extract of Scutellaria baicalensis induces semaphorin 3A production in human epidermal keratinocytes.

Project description:In a disease-state-dependent manner, the histamine-resistant itch in dry skin-based skin diseases such as atopic dermatitis (AD) and xerosis is mainly due to hyperinnervation in the epidermis. Semaphorin 3A (Sema3A) is a nerve repulsion factor expressed in keratinocytes and it suppresses nerve fiber elongation in the epidermis. Our previous studies have shown that Sema3A ointment inhibits epidermal hyperinnervation and scratching behavior and improves dermatitis scores in AD model mice. Therefore, we consider Sema3A as a key therapeutic target for improving histamine-resistant itch in AD and xerosis. This study was designed to screen a library of herbal plant extracts to discover compounds with potential to induce Sema3A in normal human epidermal keratinocytes (NHEKs) using a reporter gene assay, so that positive samples were found. Among the positive samples, only the extract of S. baicalensis was found to consistently increase Sema3A levels in cultured NHEKs in assays using quantitative real-time PCR and ELISA. In evaluation of reconstituted human epidermis models, the level of Sema3A protein in culture supernatants significantly increased by application of the extract of S. baicalensis. In addition, we investigated which components in the extract of S. baicalensis contributed to Sema3A induction and found that baicalin and baicalein markedly increased the relative luciferase activity, and that baicalein had higher induction activity than baicalin. Thus, these findings suggest that S. baicalensis extract and its compounds, baicalin and baicalein, may be promising candidates for improving histamine-resistant itch via the induction of Sema3A expression in epidermal keratinocytes.

| S-EPMC8078742 | biostudies-literature

Both Baicalein and Gallocatechin Gallate Effectively Inhibit SARS-CoV-2 Replication by Targeting Mpro and Sepsis in Mice

Project description:The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than − 6. Then, ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 5.774 ± 0.805 μM, 13.14 ± 2.081 μM and 5.158 ± 0.928 μM respectively by FRET assay. Molecular docking results also showed that ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( −)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( −)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( −)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10753-021-01602-z.

| S-EPMC8613464 | biostudies-literature

Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells.

Project description:Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.

| S-EPMC3123440 | biostudies-literature

Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots.

Project description:UNLABELLED:ETHNOPHARMACOLOGICAL RELEVANCE SCUTELLARIA BAICALENSIS: Georgi (Labiatae) is a well-known traditional Chinese medicine to treat inflammation, cardiovascular diseases, respiratory and gastrointestinal infections, etc. The present study was to understand the metabolism of the root of Scutellaria baicalensis (a.k.a. Huangqin in Chinese) in the gastrointestinal tract and the correlation between the metabolites and their respective pharmacological activities. MATERIALS AND METHODS:The water extract of the root of Scutellaria baicalensis (WESB) was incubated with simulated gastric and intestinal juices, and human fecal microflora for 24h at 37 °C. The HPLC-DAD analysis was used to monitor the in vitro metabolic process and identify its metabolites by comparing their absorption spectrum and retention time with those of chemical references. The in vitro anticomplementary and antimicrobial activity was evaluated with hemolysis assay, agar disc-diffusion method and MIC value, respectively. RESULTS:Main constituents of WESB remain unchanged during the incubation with simulated gastric juice (pH = 1.5) and intestinal juice (pH = 6.8), whereas four flavones, baicalin, wogonoside, oroxyloside and norwogonoside were metabolized into their respective aglycons by human intestinal bacteria. All four metabolites were demonstrated to have higher anticomplementary and antimicrobial activity than those of WESB. The anticomplementary active metabolites were identified to be baicalein, oroxylin A and norwogonin, among them, norwogonin is the most active compound. CONCLUSION:The presence of intestinal bacteria is demonstrated to play an important role in the gastrointestinal metabolism of WESB, and the pharmacological effects of Scutellaria baicalensis may be dependent on the intestinal bacteria metabolism.

| S-EPMC7127269 | biostudies-literature

Progress in Developing Inhibitors of SARS-CoV-2 3C-Like Protease.

Project description:Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral outbreak started in late 2019 and rapidly became a serious health threat to the global population. COVID-19 was declared a pandemic by the World Health Organization in March 2020. Several therapeutic options have been adopted to prevent the spread of the virus. Although vaccines have been developed, antivirals are still needed to combat the infection of this virus. SARS-CoV-2 is an enveloped virus, and its genome encodes polyproteins that can be processed into structural and nonstructural proteins. Maturation of viral proteins requires cleavages by proteases. Therefore, the main protease (3 chymotrypsin-like protease (3CLpro) or Mpro) encoded by the viral genome is an attractive drug target because it plays an important role in cleaving viral polyproteins into functional proteins. Inhibiting this enzyme is an efficient strategy to block viral replication. Structural studies provide valuable insight into the function of this protease and structural basis for rational inhibitor design. In this review, we describe structural studies on the main protease of SARS-CoV-2. The strategies applied in developing inhibitors of the main protease of SARS-CoV-2 and currently available protein inhibitors are summarized. Due to the availability of high-resolution structures, structure-guided drug design will play an important role in developing antivirals. The availability of high-resolution structures, potent peptidic inhibitors, and diverse compound scaffolds indicate the feasibility of developing potent protease inhibitors as antivirals for COVID-19.

| S-EPMC7463875 | biostudies-literature

Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

Project description:The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

| S-EPMC9111243 | biostudies-literature

Korean Scutellaria baicalensis Georgi flavonoid extract induces mitochondrially mediated apoptosis in human gastric cancer AGS cells.

Project description:Korean Scutellaria baicalensis Georgi has been widely used in Korean folk medicines for its range of medicinal benefits, including its anticancer effect. The aim of the present study was to investigate the underlying molecular mechanism of action of a flavonoid extract from Korean Scutellaria baicalensis Georgi (FSB) on AGS human gastric cancer cells (gastric adenocarcinoma) in which FSB exhibits an anticancer effect. Treatment of AGS cells with FSB significantly inhibited cell viability in a concentration-dependent manner. Furthermore, FSB significantly increased the proportion of cells in sub-G1 phase, and Annexin V and Hoechst 33258 fluorescent staining confirmed the apoptotic cell death. Furthermore, western blotting results identified that treatment of AGS cells with FSB significantly downregulated the expression of caspase family members, namely procaspases 3 and 9, and poly(ADP-ribose) polymerase (PARP), and subsequently upregulated cleaved caspase 3 and cleaved PARP. It was observed that FSB treatment significantly decreased the mitochondrial membrane potential of AGS cells. In addition, the ratio of the mitochondrion-associated proteins B cell lymphoma 2-associated X protein and B cell lymphoma extra large was upregulated. The results of the present study provide novel insight into the underlying molecular mechanism of the anticancer effects of FSB on AGS human gastric cancer cells and indicate that FSB may be an alternative chemotherapeutic agent for the treatment of gastric cancer.

| S-EPMC5494645 | biostudies-other

Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors.

Project description:Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents.

| S-EPMC7079562 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data