Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-o-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs

Eissa, Ibrahim H.; Alesawy, Mohamed S; Saleh, Abdulrahman M.; Alsfouk, Bshra A.; El-Attar, Abdul-Aziz M.M.; Metwaly, Ahmed M.

doi:10.3390/molecules27072287

Cited by 40 publications

(20 citation statements)

References 65 publications

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“…The protocol was adjusted to determine the most similar 10%. The default molecular properties were applied [ 86 , 87 , 88 ]. More details are available in the Supplementary Materials .…”

Section: Methodsmentioning

confidence: 99%

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Elkaeed

Eissa

Elkady

et al. 2022

IJMS

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Among a group of 310 natural antiviral natural metabolites, our team identified three compounds as the most potent natural inhibitors against the SARS-CoV-2 main protease (PDB ID: 5R84), Mpro. The identified compounds are sattazolin and caprolactin A and B. A validated multistage in silico study was conducted using several techniques. First, the molecular structures of the selected metabolites were compared with that of GWS, the co-crystallized ligand of Mpro, in a structural similarity study. The aim of this study was to determine the thirty most similar metabolites (10%) that may bind to the Mpro similar to GWS. Then, molecular docking against Mpro and pharmacophore studies led to the choice of five metabolites that exhibited good binding modes against the Mpro and good fit values against the generated pharmacophore model. Among them, three metabolites were chosen according to ADMET studies. The most promising Mpro inhibitor was determined by toxicity and DFT studies to be caprolactin A (292). Finally, molecular dynamics (MD) simulation studies were performed for caprolactin A to confirm the obtained results and understand the thermodynamic characteristics of the binding. It is hoped that the accomplished results could represent a positive step in the battle against COVID-19 through further in vitro and in vivo studies on the selected compounds.

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“…The protocol was adjusted to determine the most similar 10%. The default molecular properties were applied [ 86 , 87 , 88 ]. More details are available in the Supplementary Materials .…”

Section: Methodsmentioning

confidence: 99%

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Elkaeed

Eissa

Elkady

et al. 2022

IJMS

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“…Humans always depended on nature around them as the main source of food and medicine [21,22]. The compounds isolated from natural sources showed various bioactivities like anticancer [23][24][25][26][27], antileishmanial [28,29], antibacterial [30][31][32], neuro-protecting [33,34], antioxidant [35], and antiviral activity [36,37].…”

Section: Introductionmentioning

confidence: 99%

Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease

Youssef

Eissa

Elkady

et al. 2022

IJMS

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In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease.

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“…Our team have synthesized and examined various compounds that were designed as anti-VEGFR-2, belonging to different classes such as quinazoline [9][10][11][12], nicotinamides [13], benzoxazole [14], pyridine [15] dihydroquinolones [16], thiourea-azetidine [17,18], and quinoxaline-2 (1H)-one [19][20][21][22][23], in addition to thieno [2,3-d]pyrimidine [24]. Furthermore, our team utilized the basics of in silico chemistry as a successful tool in molecular design and docking [25,26], structural similarity [27], toxicity [28], ADMET [29], DFT [30,31], MD [32], and pharmacophore [33] investigation.…”

Section: Introductionmentioning

confidence: 99%

The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1H-Indole Derivative: In Silico and In Vitro Approaches

et al. 2022

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Corresponding to the reported features of anti-VEGFR-2-approved compounds, a new 1H-indole derivative (compound 7) was designed. The inhibitory potential of the designed compound was revealed via a molecular docking study that showed the appropriate binding. Then, MD simulation (six studies) over a period of 100 ns was performed to confirm the precise binding and optimum energy. Additionally, MM-GBSA reaffirmed the perfect binding, exhibiting a total precise energy of −40.38 Kcal/Mol. The MM-GBSA experiments named the essential amino acids in the protein–ligand interaction, employing the binding energy decomposition and revealing the diversity of interactions of compound 7 inside the VEGFR-2 enzyme. As compound 7 is new, DFT experiments were utilized for molecular structure optimization. Additionally, the DFT results validated the coherent interaction of compound 7 with the VEGFR-2 enzyme. A good value of drug-likeness of compound 7 was acknowledged via in silico ADMET studies. Interestingly, the experimental in vitro prohibitory potential of compound 7 was better than that of sorafenib, demonstrating an IC50 value of 25 nM. Notably, the strong inhibitory effects of compound 10 against two cancer cell lines (MCF-7 and HCT 116) were established with IC50 values of 12.93 and 11.52 μM, disclosing high selectivity indexes of 6.7 and 7.5, respectively.

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Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-o-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs

Cited by 40 publications

References 65 publications

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease

The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1H-Indole Derivative: In Silico and In Vitro Approaches

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