Structural analysis of EhPSP in complex with 3-phosphoglyceric acid from Entamoeba histolytica reveals a basis for its lack of phosphoglycerate mutase activity

Kumari, Poonam; Vijayan, Ramachandran; Gourinath, S.

doi:10.1016/j.ijbiomac.2021.02.153

Cited by 4 publications

(6 citation statements)

References 44 publications

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“…MM-PBSA calculations of the complexes were carried out using g_mmpbsa tool, which calculated the binding free energies of the complexes and the individual energy contributions of the residues [ 44 ]. Xmgrace (Grace 5.1.21) was used to plot the graphs [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Chemical composition and therapeutic mechanism of Xuanbai Chengqi Decoction in the treatment of COVID-19 by network pharmacology, molecular docking and molecular dynamic analysis

et al. 2022

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Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10415-7.

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Section: Methodsmentioning

confidence: 99%

Chemical composition and therapeutic mechanism of Xuanbai Chengqi Decoction in the treatment of COVID-19 by network pharmacology, molecular docking and molecular dynamic analysis

et al. 2022

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“…Next, we employed MOE docking 33,34 to calculate the binding affinity of the top 500 lead compounds. The protein was kept as rigid, and a maximum of 30 conformations for each ligand was tested, using the default parameters of MOE using Triangle Matcher placement.…”

Section: Methodsmentioning

confidence: 99%

“…To dock ligands with suitable pharmacological property, the small molecules were prefiltered by removing ligands with reactive functional groups. Next, we employed MOE docking 33,34 to calculate the binding affinity of the top 500 lead compounds. The protein was kept as rigid, and a maximum of 30 conformations for each ligand was tested, using the default parameters of MOE using Triangle Matcher placement.…”

Section: Virtual Screeningmentioning

confidence: 99%

Novel inhibitors against COVID-19 main protease suppressed viral infection

Ramachandran

Liu

et al. 2022

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause severe disease with high mortality rates, especially among older and vulnerable populations. Despite the recent success of vaccines and approval of first-generation anti-viral inhibitor against SARS-CoV-2, an expanded arsenal of anti-viral compounds that limit viral replication and ameliorate disease severity is still urgently needed in light of the continued emergence of viral variants of concern (VOC). The main protease (Mpro) of SARS-CoV-2 is the major non-structural protein required for the processing of viral polypeptides encoded by the open reading frame 1 (ORF1) and ultimately replication. Structural conservation of Mpro among SARS-CoV-2 variants make this protein an attractive target for the anti-viral inhibition by small molecules. Here, we developed a structure-based in-silico screening of approximately 11 million compounds in ZINC15 database inhibiting Mpro, which prioritized 9 lead compounds for the subsequent in vitro validation in SARS-CoV-2 replication assays using both Vero and Calu-3 cells. We validated three of these compounds significantly inhibited SARS-CoV-2 replication in the micromolar range. In summary, our study identified novel small-molecules significantly suppressed infection and replication of SARS-CoV-2 in human cells.

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“…Serine biosynthetic pathway has been extensively studied in amoeba, specifically the first two enzymes, PGDH and PSAT, − with little emphasis on the third enzyme, i.e., PSP . Recently, for the first time, our laboratory has identified and characterized PSP from Entamoeba (denoted as EhPSP) at biochemical, molecular, structural, and functional levels , and has shown its essentiality in the survival and proliferation of amoeba. The work also demonstrated that EhPSP protects the parasite from oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

“…Second, they carry out dephosphorylation reactions through distinct mechanisms, each involving different catalytic residues. Lastly, notable structural deviations were observed, and sequence conservation stands at a mere 20%, 51,63 highlighting the potential of EhPSP as a promising drug target.…”

Section: Introductionmentioning

confidence: 99%

Identification of Small Molecule Inhibitors Targeting Phosphoserine Phosphatase: A Novel Target for the Development of Antiamoebic Drugs

Kumari,

Agrawal,

Umarao

et al. 2024

ACS Omega

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Structural analysis of EhPSP in complex with 3-phosphoglyceric acid from Entamoeba histolytica reveals a basis for its lack of phosphoglycerate mutase activity

Cited by 4 publications

References 44 publications

Chemical composition and therapeutic mechanism of Xuanbai Chengqi Decoction in the treatment of COVID-19 by network pharmacology, molecular docking and molecular dynamic analysis

Chemical composition and therapeutic mechanism of Xuanbai Chengqi Decoction in the treatment of COVID-19 by network pharmacology, molecular docking and molecular dynamic analysis

Novel inhibitors against COVID-19 main protease suppressed viral infection

Identification of Small Molecule Inhibitors Targeting Phosphoserine Phosphatase: A Novel Target for the Development of Antiamoebic Drugs

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