The interaction of the bioflavonoids with five SARS-CoV-2 proteins targets: An in silico study

Mishra, Ganesh Prasad; Bhadane, Rajendra; Panigrahi, Debadash; Amawi, Haneen; Asbhy, Charles R.; Tiwari, Amit K.

doi:10.1016/j.compbiomed.2021.104464

Cited by 12 publications

(8 citation statements)

References 77 publications

(51 reference statements)

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“… 24 There was only marginal overlap between our enzymatic screening of flavonoid Mpro inhibitors and previous in silico screens. 22 Conversely, screens of small collections of flavonoids 43 , 44 or extracts of natural products 45 , 46 are far less inclusive and lack the extensive opportunity for SARs provided by enzymatic screening of a large flavonoid library. The finding that biflavones and galloylated flavonoids are enriched in Mpro inhibitors could help guide future identification and development of flavonoid-based treatments for COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication

Lin¹,

Chen²,

Scartelli³

et al. 2023

iScience

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Section: Discussionmentioning

confidence: 99%

Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication

Lin¹,

Chen²,

Scartelli³

et al. 2023

iScience

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“…Endoribonuclease (EndoU or NSP15) is a 346 residue protein with three domains namely, the N-terminal domain, middle domain, and the C-terminal domain. The N-terminal domain was found to be responsible for the formation of a hexamer, while the C-terminal domain contains the active site of the protein that facilitates replication and processing of sub-genomic RNAs 9 – 12 . It was found that NSP15 hydrolyzes the phosphodiester bond that is located at the uridine (U) sites of single and double-stranded RNA molecules.…”

Section: Introductionmentioning

confidence: 99%

Targeting SARS-CoV-2 endoribonuclease: a structure-based virtual screening supported by in vitro analysis

Ibrahim

Elfiky

Fathy

et al. 2022

Sci Rep

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Researchers are focused on discovering compounds that can interfere with the COVID-19 life cycle. One of the important non-structural proteins is endoribonuclease since it is responsible for processing viral RNA to evade detection of the host defense system. This work investigates a hierarchical structure-based virtual screening approach targeting NSP15. Different filtering approaches to predict the interactions of the compounds have been included in this study. Using a deep learning technique, we screened 823,821 compounds from five different databases (ZINC15, NCI, Drug Bank, Maybridge, and NCI Diversity set III). Subsequently, two docking protocols (extra precision and induced fit) were used to assess the binding affinity of the compounds, followed by molecular dynamic simulation supported by the MM-GBSA free binding energy. Interestingly, one compound (ZINC000104379474) from the ZINC15 database has been found to have a good binding affinity of − 7.68 kcal/Mol. The VERO-E6 cell line was used to investigate its therapeutic effect in vitro. Half-maximal cytotoxic concentration and Inhibitory concentration 50 were determined to be 0.9 mg/ml and 0.01 mg/ml, respectively; therefore, the selectivity index is 90. In conclusion, ZINC000104379474 was shown to be a good hit for targeting the virus that needs further investigations in vivo to be a drug candidate.

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“…The investigation of the binding power of the aforementioned compounds to the SARS-CoV-2 enzyme protease (6LU7) was conducted through the utilization of molecular docking strategy [ 39 , 40 ]. The generation of the three-dimensional models of the title compounds was done utilizing the builder user interface of MOE [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

El-Saghier,

Enaili,

Abdou

et al. 2023

Mol Divers

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Introduction The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed. Problem statement The SARS-CoV-2 main protease (Mpro) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of Mpro enzyme can be an effective strategy for developing new COVID-19 drugs. Methodology An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski’s rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (Mpro) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis. Findings The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from − 7.33 kcal/mol (compound 6) and − 7.22kcal/mol (compound 5) to − 6.54 kcal/mol (compounds 8 and 9). The top-ranked compounds (5 and 6) had lower HOMO–LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level. Recommendation These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications. Graphical abstract

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The interaction of the bioflavonoids with five SARS-CoV-2 proteins targets: An in silico study

Cited by 12 publications

References 77 publications

Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication

Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication

Targeting SARS-CoV-2 endoribonuclease: a structure-based virtual screening supported by in vitro analysis

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

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