Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease

Sankaran, Sandhya Karakkadparambil; Nair, Achuthsankar S.

doi:10.1080/07391102.2022.2107573

Cited by 4 publications

(1 citation statement)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After molecular docking simulation, LibDock scores calculated using Discovery Studio indicated the affinity of ligand binding to the receptor. 46 …”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Feng,

Luo,

et al. 2023

DDDT

View full text Add to dashboard Cite

Purpose YiShen HuoXue decoction (YSHXD) is a formulation that has been used clinically for the treatment of renal fibrosis (RF) for many years. We aimed to clarify therapeutic effects of YSHXD against RF and potential pharmacological mechanisms. Materials and Methods We used network pharmacology analysis and machine-learning to screen the core components and core targets of YSHXD against RF, followed by molecular docking and molecular dynamics simulations to confirm the reliability of the results. Finally, we validated the network pharmacology analysis experimentally in HK-2 cells and a rat model of RF established by unilateral ureteral ligation (UUO). Results Quercetin, kaempferol, luteolin, beta-sitosterol, wogonin, stigmasterol, isorhamnetin, baicalein, and dihydrotanshinlactone progesterone were identified as the main active components of YSHXD in the treatment of unilateral ureteral ligation-induced RF, with IL-6, IL1β, TNF, AR, and PTGS2 as core target proteins. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of YSHXD predicted by network pharmacology analysis was confirmed in HK-2 cells and UUO rats. YSHXD downregulated NLRP3, ASC, NF-κBp65, Caspase-1, GSDMD, PTGS2, IL-1β, IL-6, IL-18, TNF-α, α-SMA and upregulated HGF, effectively alleviating the RF process. Conclusion YSHXD exerts important anti-inflammatory and anti-cellular inflammatory necrosis effects by inhibiting the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, indicating that YSHXD represents a new strategy and complementary approach to RF therapy.

show abstract

“…After molecular docking simulation, LibDock scores calculated using Discovery Studio indicated the affinity of ligand binding to the receptor. 46 …”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Feng,

Luo,

et al. 2023

DDDT

View full text Add to dashboard Cite

show abstract

Molecular Dynamics and Free Energy Landscape Study of SARS‐CoV‐2 Omicron M^pro Boswellic acid Compounds of Boswellia Serrata Inhibitors

Sandhya,

Arunkumar,

Shiny

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

This work sheds light on the effect of boswellic acid compounds (Alpha boswellic acid, Beta boswellic acid, 11-keto beta boswellic acid and 3-Acetyl-11-keto beta boswellic acid) upon inhibiting SARS-CoV-2 M pro and O-M pro (Main protease). A good docking score (À 8.4 kcal/mol) is found in the case of 3-Acetyl-11-keto beta boswellic acid as compared to the reference and three other boswellic acid compounds. ADMET results suggest that all these compounds are nontoxic and their pharmacokinetic properties are satisfactory. Moreover, a stability analysis with M pro /O-M pro through RMSD, RMSF, hydrogen bonds and Rg parameters in MD simulations is made and we found better values than the reference case. Pre and post-MD structures of Ligands-M pro show a similar binding site whereas a drift can be noted for L-O-M pro . 3-Acetyl-11-keto beta boswellic acid shows an average of five hydrogen bonds and it remains stable within the binding pocket of M pro during the simulation period in comparison to other boswellic acids compounds. Various metastable conformations are observed for all compounds in FEL (free energy landscape), however, Acyclovir-M pro , Alpha boswellic acid-M pro and Beta boswellic acid-O-M pro display only one global minimum. The results suggest that these compounds can be used as potential lead molecules for breakthroughs in drug discovery.

show abstract

Genome-wide characterization and expression of Oryza sativa AP2 transcription factor genes associated with the metabolism of mesotrione

Chen,

Shi,

et al. 2024

Chem. Biol. Technol. Agric.

View full text Add to dashboard Cite

Background The APETALA2 (AP2) transcription factor (TF) superfamily, one of the largest gene families in plants, plays an essential role in regulating plant growth and their stress responses. However, the role of AP2 in rice under pesticide stress remains unclear. To investigate the characteristics and functions of the rice AP2 gene family under pesticide stress, the expression of 105 AP2-coding genes and 26 AP2 differentially expressed genes (DEGs) were identified in mesotrione (MTR)-treated rice transcriptome datasets. Results Three subfamilies of the AP2 gene family (AP2/ERF, RAV, and soloists) were identified using sequence alignment and phylogenetic analysis. Chromosome location analysis revealed that the 26 rice AP2 DEGs were unevenly distributed on 10 of the 12 rice chromosomes, and segmental duplication contributed to the expansion of Oryza sativa AP2 (OsAP2) gene family. Collinearity analyses demonstrated that rice AP2 genes displayed 16 orthologous gene pairs, and 12 and 26 orthologous gene pairs were shared of Arabidopsis and soybean, respectively. In addition, rice AP2 genes featured various gene structures, cis-elements, motif compositions, and conserved domains that allowed them to encode genes that elicit biotic and abiotic stress responses. An analysis of docking between MTR and six AP2 DEGs revealed amino acid residues involved in MTR binding. Quantitative reverse transcription–polymerase chain reaction verified that several AP2 genes were preferentially expressed during MTR-induced stress. The roles of OsAP2 proteins in MTR metabolism were further supported by protein–protein interaction network analysis, which illustrated how these proteins interact with target proteins. Conclusion The initial findings of this study define the features of the OsAP2 superfamily and offer important tools for functional analyses of OsAP2 genes implicated in the metabolism of MTR. Graphical Abstract

show abstract

Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease

Cited by 4 publications

References 60 publications

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Molecular Dynamics and Free Energy Landscape Study of SARS‐CoV‐2 Omicron M^pro Boswellic acid Compounds of Boswellia Serrata Inhibitors

Genome-wide characterization and expression of Oryza sativa AP2 transcription factor genes associated with the metabolism of mesotrione

Contact Info

Product

Resources

About

Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease

Cited by 4 publications

References 60 publications

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Molecular Dynamics and Free Energy Landscape Study of SARS‐CoV‐2 Omicron Mpro Boswellic acid Compounds of Boswellia Serrata Inhibitors

Genome-wide characterization and expression of Oryza sativa AP2 transcription factor genes associated with the metabolism of mesotrione

Contact Info

Product

Resources

About

Molecular Dynamics and Free Energy Landscape Study of SARS‐CoV‐2 Omicron M^pro Boswellic acid Compounds of Boswellia Serrata Inhibitors