1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates

Kavitha, K.; Sivakumar, Subramaniam; Ramesh, Balasubramanian

doi:10.1016/j.bpc.2020.106478

Cited by 21 publications

(5 citation statements)

References 56 publications

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“…as SARS-CoV-2 main protease inhibitors [5], and as antimicrobials [6,7]. Additionally, it is believed that triazolopyrimidines are promising candidates for treating Alzheimer's disease and related neurodegenerative tauopathies [8].…”

Section: Introductionmentioning

confidence: 99%

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

et al. 2021

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Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

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Section: Introductionmentioning

confidence: 99%

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

et al. 2021

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“…32 Cys-145, Glu-166, and His-163 were the most attractive residue of SARS-CoV-2 M pro to form hydrogen bonds. [32][33][34] The location of M pro substrate-binding site was between domains I and II, which was Cys-145 and His-41 were catalytic activity site. [32][33][34][35] In line with this study which M pro binds to apigenin, chrysin, and quercetin in Cys-145.…”

Section: Docking Visualizationmentioning

confidence: 99%

“…[32][33][34] The location of M pro substrate-binding site was between domains I and II, which was Cys-145 and His-41 were catalytic activity site. [32][33][34][35] In line with this study which M pro binds to apigenin, chrysin, and quercetin in Cys-145. Besides M pro , RdRp also plays a pivotal role in the viral life cycle.…”

Section: Docking Visualizationmentioning

confidence: 99%

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In Silico Study of Entry Inhibitor from Moringa oleifera Bioactive Compounds against SARS-CoV-2 Infection

Mawaddani¹,

Sutiyanti²,

Widyananda³

et al. 2022

Pharmacogn J.

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Pterygospermin, Quercetin, Rutin, and β-amyrin which has an antiviral potential compounds against COVID 19 by inhibiting M pro and RdRp activity. [15][16][17][18] Besides all the compounds above, Oleic acid was most found at around 84% in M. Oleifera. 19 M. oleifera was the most appropriate candidate for an antiviral agent against SARS-CoV-2. The aim of this study was to screen bioactive compounds of Moringa oleifera and to identify the antiviral potential compounds toward SARS-CoV-2 through an entry inhibitor mechanism. METHODS Data mining of sampleThe bioactive compounds of M. oleifera which consist of anthraquinone, apigenin, aurantiamide acetate, benzyl isothiocyanate, chlorogenic acid, chrysin, dibutyl phthalate, ellagic acid, hesperidin, isorhoifolin, myricetin, pterygospermin, quercetin, rutin, and vitex. The bioactive compounds of M. oleifera were retrieved format from PubChem database (https://pubchem.ncbi.nlm.nih.gov/) in sdf format. 20 Protein modelingThe structure of M pro and RdRp as the target proteins which were not available in the RCSB PDB database was modeled based on their amino acid sequence. The NCBI (https://www.ncbi.nlm.nih.gov/) database was used to retrieve sequences of amino acids with fasta format. Furthermore, protein modeling is made through the SWISSMODEL site (https://swissmodel. expasy.org/). The selection of protein models was selected from several parameters such as QMQE value, QMEAN value, coverage value, local quality value, and comparison plot. In addition, the protein

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“…By using desmond modules of the Schrodinger 2020-2 suite software molecular dynamics simulation study of protein-ligand complex was carried to analyze the ligand consistency and the binding mode stability in the binding pocket of protein [51]. Top candidates with good docking results were carried for MD simulation to know the compound stability with spike binding domain with Main protease (6LU7) and spike binding domain with ACE2 receptor (6M0J) of Sars-CoV-2.…”

Section: Molecular Dynamicsmentioning

confidence: 99%

Phytochemicals of Citrus Fruits: The in-silico Investigation against Sars-CoV-2 Proteins

Jayaprakash¹,

Renganathan

Shanthappa³

et al. 2022

Trends Sci

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The current pandemic Covid-19 brought about by a newly emerged and highly infectious virus named as Sars-CoV-2 as a worldwide danger, has infected more than 600 million people and number of deaths are continuously rising day by day. Till date there are no medications accessible for treatment. All over the world scientists and researchers are involved in the study of this emerged virus and its lifecycle. Structures of proteins in the life cycle of virus has been revealed in RCSB PDB (Research Collaboratory for Structural Bioinformatics Protein Data Bank) by researchers. Citrus fruits are used to treat many distresses of humans. Literature survey shows that it has various activities. Our research work is meant to identify the phytoconstituents which are having phenolic composition and good antiviral and antioxidant properties from citrus fruits against Covid-19 proteins (spike binding domain with ACE2 receptor and spike binding domain with Main protease) and to know its in-silico molecular basis. In this study, about 25 compounds from citrus fruits which is having a good antiviral and antioxidant properties and also phenolic composition were employed for molecular docking analysis, molecular dynamic simulation studies and ADME studies. Based on present study 2 compounds from Citrus fruits acted well against the Covid-19 proteins. The MD simulations were employed to identify Hesperidin and Procyanidin B2 as hit compounds. Further ADME analysis were studied for top 2 compounds, these compounds can be further taken for in-vitro studies to know the effective activity against Covid-19. HIGHLIGHTS Citrus fruit phytochemicals are fascinating core, which shows an excellent anti-viral, anti-inflammatory and antioxidant properties The SARS-CoV-2 is newly emerged and highly infectious virus, has infected more than 600 million people and number of deaths are continuously rising day by day Molecular docking analysis, Molecular dynamics simulation ADME studies was carried out Compound Hesperidin and Procyanidin B2 showed a good inhibitory activity against SARS-CoV-2 proteins GRAPHICAL ABSTRACT

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1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates

Cited by 21 publications

References 56 publications

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

In Silico Study of Entry Inhibitor from Moringa oleifera Bioactive Compounds against SARS-CoV-2 Infection

Phytochemicals of Citrus Fruits: The in-silico Investigation against Sars-CoV-2 Proteins

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