Potential Exploration of Recent FDA-Approved Anticancer Drugs Against Models of SARS-CoV-2’s Main Protease and Spike Glycoprotein: A Computational Study

COVID-19 has become a worldwide risk to the healthcare system of practically every nation of the world, which originated from Wuhan, China. To date, no specific drugs are available to treat this disease. The exact source of the SARS-CoV-2 is yet unknown, although the early cases are associated with the Seafood market in Huanan, South China. This manuscript reports the in silico molecular modeling of recent FDA-approved anticancer drugs (Capmatinib, Pemigatinib, Selpercatinib, and Tucatinib) for their inhibitory action against COVID-19 targets. The selected anticancer drugs are docked on SARS-CoV-2 main protease (PDB ID: 6LU7) and SARS-CoV-2 spike glycoprotein (PDB ID: 6M0J) to ascertain the binding ability of these drugs. ADMET parameters of the drugs are assessed, and in addition, DFT calculations are done to investigate the pharmacokinetics, thermal parameters, dipole moments, and chemical reactivity descriptors. The docking energies (ΔG) and the interacting amino acid residues are discussed. Promising molecular docking conclusions have been accomplished, which demonstrated the potential of selected anticancer drugs for plausible drug development to fight COVID-19. Further optimizations with the drug may support the much-needed rapid response to mitigate the pandemic.

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Computational peptidology approach to the study of the chemical reactivity and bioactivity properties of Aspergillipeptide D, a cyclopentapeptide of marine origin

Scientific Reports ◽

10.1038/s41598-021-04513-z ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Norma Flores-Holguín ◽

Juan Frau ◽

Daniel Glossman-Mitnik

Keyword(s):

Density Functional ◽

Computational Study ◽

Chemical Reactivity ◽

Therapeutic Drug ◽

Moderate Activity ◽

Conceptual Density Functional Theory ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

Aspergillus Sp

AbstractAspergillipeptide D is a cyclic pentapeptide isolated from the marine gorgonian Melitodes squamata-derived fungus Aspergillus sp. SCSIO 41501 that it has been shown to present moderate activity against herpes virus simplex type 1 (HSV-1). Thus, this paper presents the results of a computational study of this cyclopentapeptide’s chemical reactivity and bioactivity properties using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from combining chemical reactivity descriptors derived from Conceptual Density Functional Theory (CDFT) and some Cheminformatics tools which may be used. This results in an improvement of the virtual screening procedure by a similarity search allowing the identification and validation of the known ability of the peptide to act as a possible useful drug. This was followed by an examination of the drug’s bioactivity and pharmacokinetics indices in relation to the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. The findings provide further evidence of the MN12SX density functional’s superiority in proving the Janak and Ionization Energy theorems using the proposed KID approach. This has proven to be beneficial in accurately predicting CDFT reactivity characteristics, which aid in the understanding of chemical reactivity. The Computational Pharmacokinetics study revealed the potential ability of Aspergillipeptide D as a therapeutic drug through the interaction with different target receptors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

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A CDFT-Based Computational Peptidology (CDFT-CP) Study of the Chemical Reactivity and Bioactivity of the Marine-Derived Alternaramide Cyclopentadepsipeptide

Journal of Chemistry ◽

10.1155/2021/2989611 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Norma Flores-Holguín ◽

Juan Frau ◽

Daniel Glossman-Mitnik

Keyword(s):

Density Functional ◽

Computational Study ◽

Chemical Reactivity ◽

Therapeutic Drug ◽

Inhibitory Effects ◽

Conceptual Density Functional Theory ◽

Functional Theory ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

And Staphylococcus Aureus

Alternaramide is a cyclic pentadepsipeptide isolated from marine sources that has been shown to present weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus as well as inhibitory effects on inflammatory mediator expressions. Thus, this work reports the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide considering a CDFT-based computational peptidology (CDFT-CP) methodology that results from the combination of the chemical reactivity descriptors that arise from conceptual density functional theory (CDFT) together with some cheminformatics tools that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. The results represent a new confirmation of the superiority of the MN12SX density functional in the fulfilment of the Janak and ionization energy theorems through the proposed KID procedure. This has been useful for the accurate prediction of the CDFT reactivity descriptors that help in understanding the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of alternaramide as a therapeutic drug by interacting with GPCR ligands and protease inhibitors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

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Chemical Reactivity Descriptors and Molecular Docking Studies of Octyl 6-O-hexanoyl-β-D-glucopyranosides

Journal of Applied Science & Process Engineering ◽

10.33736/jaspe.3727.2021 ◽

2021 ◽

Vol 8 (2) ◽

pp. 903-912

Author(s):

Naimul Islam ◽

Mohammad H.O. Roshid ◽

Md. Lutfor Rahaman

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Chemical Reactivity ◽

Ester Group ◽

Docking Studies ◽

Urate Oxidase ◽

Reactivity Descriptors ◽

Main Protease ◽

Chemical Reactivity Descriptors ◽

Homo Lumo

The present study describes different chemical reactivity predictions of 6-O-hexanoylation of octyl β-D-glucopyranosides prepared from octyl β-D-glucopyranoside (OBG). Also, molecular docking of the OBGs was conducted against SARS-CoV-2 main protease (6LU7), urate oxidase (Aspergillus flavus; 1R51) and glucoamylase (Aspergillus niger; 1KUL). DFT optimization indicated that glucoside 1 and its ester derivatives 2-7 exist in 4C1 conformation with C1 symmetry. Interestingly, the addition of ester group(s) decreased the HOMO-LUMO gap (Δԑ) of glucosides indicating their good chemical reactivities, whereas the other chemical reactivity descriptors indicated their moderate reactive nature. This fact of moderate reactivity was confirmed by their molecular docking with 6LU7, 1R51 and 1KUL. All the esters showed a moderate binding affinity with these three proteins. More importantly, incorporation of the ester group(s) increased binding affinity with 6LU7 and 1R51, whereas decreased with 1KUL as compared to non-ester OBG 1.

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Theoretical Study of the Reaction of Formation of Some Free Phosphines by Stereoselective Hydrophosphination through DFT Method

Asian Journal of Applied Chemistry Research ◽

10.9734/ajacr/2018/v1i29638 ◽

2018 ◽

pp. 1-10

Author(s):

Kouadio Valery Bohoussou ◽

Anoubilé Bénié ◽

Mamadou Guy-Richard Koné ◽

N’guessan Yao Silvère Diki ◽

Kafoumba Bamba ◽

...

Keyword(s):

Theoretical Study ◽

Chemical Reactivity ◽

Dft Method ◽

Trans Form ◽

Dft Methods ◽

Activation Barriers ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

Theoretical Results ◽

Cis Isomer

In this work the formation of vinylphosphines was studied through the hydrophosphination reaction. The study aims to rationalize the stereoselectivity of these compounds using quantum DFT methods. This theoretical study of chemical reactivity was conducted at B3LYP/6-311 + G (d, p) level. Global chemical reactivity descriptors, stationary point energies and activation barriers were examined to foretell the relative stability of the stereoisomers formed. The various results obtained have revealed that the addition of arylphosphine to dihalogenoacetylene is stereospecific. The Trans form of vinylphosphines is more stable than the Cis form, when the substituent on phosphorus generates less or no π-conjugations. On the other hand, the Cis isomer is predominant when the aryl radical favors more π-conjugations. The theoretical results obtained are in agreement with the experimental results.

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Chemical Reactivity Descriptors for Ambiphilic Reagents: Dual Descriptor, Local Hypersoftness, and Electrostatic Potential

The Journal of Physical Chemistry A ◽

10.1021/jp902792n ◽

2009 ◽

Vol 113 (30) ◽

pp. 8660-8667 ◽

Cited By ~ 120

Author(s):

Carlos Cárdenas ◽

Nataly Rabi ◽

Paul W. Ayers ◽

Christophe Morell ◽

Paula Jaramillo ◽

...

Keyword(s):

Electrostatic Potential ◽

Chemical Reactivity ◽

Dual Descriptor ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors

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New molecular target insights about protein kinases of the Plasmodium falciparum. Using molecular docking and DFT-based reactivity descriptors

Journal of Theoretical and Computational Chemistry ◽

10.1142/s0219633617500766 ◽

2017 ◽

Vol 16 (08) ◽

pp. 1750076 ◽

Cited By ~ 1

Author(s):

Alejandro Morales-Bayuelo

Keyword(s):

Plasmodium Falciparum ◽

Protein Kinases ◽

Density Functional ◽

Chemical Potential ◽

Chemical Reactivity ◽

Binding Pocket ◽

Fukui Functions ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

Hinge Zone

Currently, there is increasing interest in the potential of malaria inhibitors in Plasmodium falciparum activity. In this work, is propose a possible alternative to classifying 154 antimalarials, with P. falciparum activity. These antimalarials were synthesized by the Chibale’s group ( http://www.kellychibaleresearch.uct.ac.za/ ), with the goal of finding new insights on the binding pocket of the protein kinase PfPK5, PfPK7, PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 of the malaria parasite. However, there is only information about crystallography of PfPK5 and PfPK7. The protein kinases PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 were modeled using molecular homology. The validation used shows that our homology models can be an alternative for the protein kinases from P. falciparum, unknown today. The antimalarials were classified by taking into account the interactions in the hinge zone. These ligands bind to the kinase through the formation of one of two hydrogen bonds, with the backbone residues of the hinge region connecting the kinase N- and C-terminal loops. These interactions were supported by a reactivity chemistry analysis, using global chemical reactivity descriptors such as chemical potential, hardness, softness, electrophilicity, and the Fukui functions as local reactivity descriptors, within the Density Functional Theory (DFT) context.

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Computational Nutraceutics: Chemical Reactivity Properties of the Flavonoid Naringin by Means of Conceptual DFT

Journal of Chemistry ◽

10.1155/2013/850297 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Jorge Ignacio Martínez-Araya ◽

Guillermo Salgado-Morán ◽

Daniel Glossman-Mitnik

Keyword(s):

Active Sites ◽

Chemical Reactivity ◽

Fukui Function ◽

Conceptual Dft ◽

Density Functionals ◽

Structure And Properties ◽

Dual Descriptor ◽

Reactivity Descriptors ◽

Koopmans Theorem ◽

Chemical Reactivity Descriptors

The M06 family of density functionals has been assessed for the calculation of the molecular structure and properties of the Naringin molecule. The chemical reactivity descriptors have been calculated through Conceptual DFT. The active sites for nucleophilic and electrophilic attacks have been chosen by relating them to the Fukui function indices and the dual descriptorf(2)(r). A comparison between the descriptors calculated through vertical energy values and those arising from the Koopmans' theorem approximation has been performed in order to check for the validity of the last procedure.

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Chemical Reactivity Properties, Solubilities, and Bioactivity Scores of Some Pigments Derived from Carotenoids of Marine Origin through Conceptual DFT Descriptors

Journal of Chemistry ◽

10.1155/2019/9624108 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Norma Flores-Holguín ◽

Juan Frau ◽

Daniel Glossman-Mitnik

Keyword(s):

Density Functional ◽

Chemical Reactivity ◽

Basis Set ◽

Carotenoid Pigments ◽

Density Functionals ◽

Solvation Model ◽

Conceptual Density Functional Theory ◽

Functional Theory ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors

Five density functionals, CAM-B3LYP, LC-ωHPBE, MN12SX, N12SX, and ωB97XD, in connection with the Def2TZVP basis set were assessed together with the SMD solvation model for the calculation of the molecular properties, chemical reactivities, and solubilities of some pigments derived from astaxanthin, β-cryptoxanthin, fucoxanthin, myxol, siphonaxanthin, siphonein, and zeaxanthin marine carotenoids in the presence of different solvents (hexane, methanol, ethanol, and water). All the chemical reactivity descriptors for the systems were calculated via conceptual density functional theory (CDFT). Finally, the potential bioavailability and druggability as well as the bioactivity scores for the marine carotenoid pigments were predicted through different methodologies already reported in the literature, which have been previously validated during the study of other natural products obtained from marine sources.

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