<i>In silico</i> strategies for modeling RNA aptamers and predicting binding sites of their molecular targets

Escamilla-Gutiérrez, Alejandro; Ribas‐Aparicio, Rosa María; Córdova-Espinoza, María Guadalupe; Castelán-Vega, Juan Arturo

doi:10.1080/15257770.2021.1951754

Cited by 22 publications

(16 citation statements)

References 23 publications

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“…To measure the similarity of two objects, their general features have to be compared. On a molecular level, the molecular features or descriptors of any compound start from the general physicochemical properties and extend to more specific structural features such as partition coefficient (ALog p) [57], molecular weight (M. Wt) [58], hydrogen bond donors (HBA) [59], hydrogen bond acceptors (HBD) [60], number of rotatable bonds [61], number of rings, and also aromatic rings [62], in addition to molecular fractional polar surface area (MFPSA) [63].…”

Section: Molecular Similarity Against Sammentioning

confidence: 99%

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

et al. 2021

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In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.

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Section: Molecular Similarity Against Sammentioning

confidence: 99%

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

et al. 2021

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“…The examined descriptors are of a molecular type, such as molecular weight (M.W.) [ 50 ], hydrogen bond donors (HBA) [ 51 ], hydrogen bond acceptors (HBD) [ 52 ], partition coefficient (ALog p), which is the ratio of the concentration of a substance in the lipid phase to the concentration in the aqueous phase when the two concentrations are at equilibrium [ 53 ], number of rotatable bonds [ 54 ], number of rings, and aromatic rings [ 55 ], as well as the molecular fractional polar surface area (MFPSA) [ 56 ]. The examined compound is represented as a binary array (number of binary bits) to be computed.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′-o-methyltransferase (2′OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2′-o-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach. At the beginning, molecular fingerprints experiment with SAM (S-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. Then, a structural similarity experiment recommended 26 compounds. Therefore, the 26 compounds were docked against 2′OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, (1187), Calcium folinate (1913), Raltegravir (1995), Regadenoson (2176), Ertapenem (2396), Methylergometrine (2532), and Thiamine pyrophosphate hydrochloride (2612)). Out of the docked ligands, Ertapenem (2396) showed an ideal binding mode like that of the co-crystallized ligand (SAM). It occupied all sub-pockets of the active site and bound the crucial amino acids. Accordingly, some MD simulation experiments (RMSD, RMSF, Rg, SASA, and H-bonding) have been conducted for the 2′OMTase—Ertapenem complex over 100 ns. The performed MD experiments verified the correct binding mode of Ertapenem against 2′OMTase exhibiting low energy and optimal dynamics. Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of −43 KJ/mol. Furthermore, the binding free energy analysis revealed the essential amino acids of 2′OMTase that served positively to the binding. The achieved results bring hope to find a treatment for COVID-19 via in vitro and in vivo studies for the pointed compounds.

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“…The Discovery Studio software investigated the subsequent molecular descriptors in jusan coumarin and the examined ligands; the partition coefficient, ALog p, [ 70 ]; the molecular weight, M. W, [ 71 ]; the number of atoms that act as H- bond donors (HBD) [ 72 ]; and H- bond acceptors (HBA) [ 73 ]; the rotatable bonds numbers [ 74 ]; the aromatic rings numbers [ 75 ]; and the heterocyclic rings numbers [ 76 ] together with the molecular fractional polar surface area (MFPSA) [ 77 ]. The outputs demonstrated the great degree of similarity between jusan coumarin and the co-crystallized ligands ( X77 ) of SARS-CoV-2 main protease (PDB ID: 6W63) ( Table 2 and Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from Artemisia glauca

et al. 2022

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A new dicoumarin, jusan coumarin, (1), has been isolated from Artemisia glauca aerial parts. The chemical structure of jusan coumarin was estimated, by 1D, 2D NMR as well as HR-Ms spectroscopic methods, to be 7-hydroxy-6-methoxy-3-[(2-oxo-2H-chromen-6-yl)oxy]-2H-chromen-2-one. As the first time to be introduced in nature, its potential against SARS-CoV-2 has been estimated using various in silico methods. Molecular similarity and fingerprints experiments have been utilized for 1 against nine co-crystallized ligands of COVID-19 vital proteins. The results declared a great similarity between Jusan Coumarin and X77, the ligand of COVID-19 main protease (PDB ID: 6W63), Mpro. To authenticate the obtained outputs, a DFT experiment was achieved to confirm the similarity of X77 and 1. Consequently, 1 was docked against Mpro. The results clarified that 1 bonded in a correct way inside Mpro active site, with a binding energy of −18.45 kcal/mol. Furthermore, the ADMET and toxicity profiles of 1 were evaluated and showed the safety of 1 and its likeness to be a drug. Finally, to confirm the binding and understand the thermodynamic characters between 1 and Mpro, several molecular dynamics (MD) simulations studies have been administered. Additionally, the known coumarin derivative, 7-isopentenyloxycoumarin (2), has been isolated as well as β-sitosterol (3).

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In silico strategies for modeling RNA aptamers and predicting binding sites of their molecular targets

Cited by 22 publications

References 23 publications

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

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

Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from Artemisia glauca

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