SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking

Cao, Thao Quyen; Kim, Jeong Ah; Woo, Mi Hee; Min, Byung Sun

doi:10.1016/j.bmcl.2021.127972

Cited by 13 publications

(12 citation statements)

References 41 publications

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“…Perhaps the most common misinterpretation of computational studies related to SARS-CoV-2 is taking molecular docking results as a demonstration of ligand binding . Examples of this can be found in the scientific literature, particularly in reports where a few plant-derived compounds are docked into the Mpro and/or PLpro enzymes, and authors claimed that the top-scoring ones are enzyme inhibitors. ,− We understand that not all research groups have the capability of experimentally testing their predictions. However, some theoretical options could add additional support to computational studies, making them attractive for groups who do have the capacity for performing experimental evaluations.…”

Section: Resultsmentioning

confidence: 99%

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

et al. 2022

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Ever since coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, was declared a pandemic on March 11, 2020, by the WHO, a concerted effort has been made to find compounds capable of acting on the virus and preventing its replication. In this context, researchers have refocused part of their attention on certain natural compounds that have shown promising effects on the virus. Considering the importance of this topic in the current context, this study aimed to present a critical review and analysis of the main reports of plant-derived compounds as possible inhibitors of the two SARS-CoV-2 proteases: main protease (Mpro) and Papain-like protease (PLpro). From the search in the PubMed database, a total of 165 published articles were found that met the search patterns. A total of 590 unique molecules were identified from a total of 122 articles as potential protease inhibitors. At the same time, 114 molecules reported as natural products and with annotation of theoretical support and antiviral effects were extracted from the COVID-19 Help database. After combining the molecules extracted from articles and those obtained from the database, we identified 648 unique molecules predicted as potential inhibitors of Mpro and/or PLpro. According to our results, several of the predicted compounds with higher theoretical confidence are present in many plants used in traditional medicine and even food, such as flavonoids, carboxylic acids, phenolic acids, triterpenes, terpenes phytosterols, and triterpenoids. These are potential inhibitors of Mpro and PLpro. Although the predictions of several molecules against SARS-CoV-2 are promising, little experimental information was found regarding certain families of compounds. Only 45 out of the 648 unique molecules have experimental data validating them as inhibitors of Mpro or PLpro, with the most frequent scaffold present in these 45 compounds being the flavone. The novelty of this work lies in the analysis of the structural diversity of the chemical space among the molecules predicted as inhibitors of SARS-CoV-2 Mpro and PLpro proteases and the comparison to those molecules experimentally validated. This work emphasizes the need for experimental validation of certain families of compounds, preferentially combining classical enzymatic assays with interaction-based methods. Furthermore, we recommend checking the presence of Pan-Assay Interference Compounds (PAINS) and the presence of molecules previously reported as inhibitors of Mpro or PLpro to optimize resources and time in the discovery of new SARS-CoV-2 antivirals from plant-derived molecules.

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Section: Resultsmentioning

confidence: 99%

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

et al. 2022

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“…Recently several studies used PyRx software particularly for SARS-CoV2 protease inhibition studies using molecular docking [27]. PyRx is a computational drug discovery virtual screening software which can be used to test chemical compounds against possible therapeutic drug targets.…”

Section: Molecular Docking Of the Compounds Against Rdrp Structurementioning

confidence: 99%

“…The pharmacophores of ligand molecules and receptors, as well as mathematical force field functions, are used to calculate binding affinity [29,30] . All the 24 compounds were loaded along with the RdRp protein and after docking, based on binding affinity and RMSD values the compounds were further screened to 10 for further interactions visualization [27,30].…”

Section: Molecular Docking Of the Compounds Against Rdrp Structurementioning

confidence: 99%

In-silico ADME and Docking-based Virtual Screening Study Aiming at the Sigma-Covalent Inhibition of SARS-CoV-2 RdRp

Reddy

Phavethra

et al. 2021

JPRI

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The objectives of the study were to examine the virtual screening of the compounds and sigma-covalent inhibition of SARS-CoV-2 RdRp (RNA-Dependent RNA-Polymerase), which is conserved and is an essential enzyme for RNA transcription and replication of this virus. In this study, we collected around 1225 similar compounds of Penciclovir and Acyclovir inhibitors from PubChem and predicted ADME (Adsorption, Distribution, Metabolism and Excretion) molecular descriptors using Swiss-ADME server. Virtually screened 24/1225 compounds based on drug-likeliness five rules (Lipinski, Ghose, Veber, Egan, and Muegge) and lead-likeliness properties. Further 10/24 compounds screened, based on high binding affinity and RMSD<3.5Å against RdRp structure using PyRx docking software. Furthermore, the molecular interactions of 10 compounds studied using Discovery studio software and finally screened five PubChem compounds 57201841, 135408972, 54552823, 135409422 and 467850, based on bioactivity score using Molinsipiration cheminformatics software. All these five compounds showed up anti-SARS CoV-2 activity, though further in-vitro studies are required.

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“…Phenanthrenes are relatively rare, secondary metabolites derived through the formation of the oxidative coupling of the aromatic rings of stilbene precursors. More than 200 phenanthrenes have been isolated from plants belonging to the Annonaceae, Aristolochiaceae, Cannabaceae, Combretaceae, Cucurbitaceae, Dioscorea ceae, Euphorbiaceae, and Stemonaceae families [ 1 , 2 ]. Phenanthrenes that have been isolated so far can be classified into three major groups by differences in their substitutents, which include monophenanthrenes, diphenanthrenes, and triphenanthrenes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of Quantitative Analysis Method for Phenanthrenes in Peels of the Dioscorea Genus

Kim

Cao

Yeo

et al. 2022

J. Microbiol. Biotechnol.

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Phenanthrenes are bioactive phenolic compounds found in genus Dioscorea, in which they are distributed more in peel than in flesh. Recent studies on phenanthrenes from Dioscorea sp. peels have revealed the potential for valuable biomaterials. Herein, an analytical method using highperformance liquid chromatography (HPLC) for quantitation of bioactive phenanthrenes was developed and validated. The calibration curves were obtained using the phenanthrenes (1-3) previously isolated from Dioscorea batatas concentrations in the range of 0.625-20.00 μg/ml with a satisfactory coefficient of determination (R 2 ) of 0.999. The limit of detection (LOD) and the limit of quantification (LOQ) values of the isolated phenanthrenes ranged from 0.78-0.89 and 2.38-2.71 μg/ml, respectively. The intraday and interday precision ranged from 0.25-7.58%. The recoveries of the isolated phenanthrenes were from 95 to 100% at concentrations of 1.25, 2.5, and 5.0 μg/ml. Additionally, phenanthrenes (1-3) were found in all investigated peel extracts. Hence, the developed method was encouraging for the quantitative analysis of phenanthrenes in genus Dioscorea.

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SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking

Abstract: Graphical abstract

Cited by 13 publications

References 41 publications

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

In-silico ADME and Docking-based Virtual Screening Study Aiming at the Sigma-Covalent Inhibition of SARS-CoV-2 RdRp

Development and Validation of Quantitative Analysis Method for Phenanthrenes in Peels of the Dioscorea Genus

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