Missense mutations involvement in COX-2 structure, and protein-substrate binding affinity: in-silico study

Background: The Covid-19 virus emerged a few months ago in China and infections rapidly escalated into a pandemic. Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. Method: In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. Result: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

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IN SILICO STUDY OF APIGENIN AND APIGETRIN AS INHIBITOR OF 3-HYDROXY-3-METHYL-GLUTAYL-COENZYME A REDUCTASE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.20493 ◽

2017 ◽

Vol 10 (11) ◽

pp. 284

Author(s):

Dwintha Lestari ◽

Elin Yulinah Sukandar ◽

Irda Fidrianny

Keyword(s):

Binding Site ◽

Binding Affinity ◽

In Silico ◽

Coenzyme A ◽

Inhibition Constant ◽

Two Dimensional ◽

Binding Interaction ◽

Docking Result ◽

Binding Process ◽

In Silico Study

Objective: The objectives of this research were to investigate in silico interaction between apigenin and apigetrin with 3-hydroxy-3-methyl-glutayl-coenzyme A (HMG Co-A) reductase, to find the most favorable binding site as well as to predict the binding mode.Materials and Methods: Docking calculation was performed by branded Sony Vaio PC Linux Ubuntu 14.04 LTS. The binding process based on the best docking result with HMG Co-A reductase was presented in two-dimensional diagram. Statin, atorvastatin, and R-mevalonate were used as standard.Results: Binding affinity and inhibition constant of R-mevalonate were Ei=−4.2 kcal/mol, Ki=836.78 μM; apigenin Ei=−7.0 kcal/mol, Ki=7.43 μM; apigetrin Ei=−5.9 kcal/mol, Ki=47.53 μM; simvastatin Ei=−8.2 kcal/mol; Ki=0.98 μM; atorvastatin Ei=−8.4 kcal/mol; Ki=0.7 μM. Apigenin had better binding interaction than apigetrin.Conclusion: Apigenin could be developed as anticholesterol.

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Polymorphism in the ligand binding domain of rage alters its binding affinity towards Aβ42 peptides: an in-silico study

International Journal of Bioinformatics Research and Applications ◽

10.1504/ijbra.2016.078226 ◽

2016 ◽

Vol 12 (3) ◽

pp. 181

Author(s):

Sreeram Krishnan ◽

P. Rani

Keyword(s):

Ligand Binding ◽

Binding Affinity ◽

In Silico ◽

Binding Domain ◽

Ligand Binding Domain ◽

In Silico Study

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Cytotoxic activity of andrographolide in colon cancer through inhibition cox-2 by in silico study

Journal of Physics Conference Series ◽

10.1088/1742-6596/1040/1/012009 ◽

2018 ◽

Vol 1040 ◽

pp. 012009 ◽

Cited By ~ 1

Author(s):

N P L Laksmiani ◽

K R Reynaldi ◽

M I Widiastari ◽

I P W Nugraha ◽

I M K Suyadnya ◽

...

Keyword(s):

Colon Cancer ◽

Cytotoxic Activity ◽

In Silico ◽

In Silico Study ◽

Cox 2

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In silico study on the substrate binding manner in human myo-inositol monophosphatase 2

Journal of Molecular Modeling ◽

10.1007/s00894-010-0937-8 ◽

2011 ◽

Vol 17 (10) ◽

pp. 2559-2567 ◽

Cited By ~ 4

Author(s):

Seisuke Fujita ◽

Tetsuo Ohnishi ◽

Shujiro Okuda ◽

Ryo Kobayashi ◽

Satoshi Fukuno ◽

...

Keyword(s):

In Silico ◽

Substrate Binding ◽

Inositol Monophosphatase ◽

In Silico Study

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In-silico molecular docking analysis of some plant derived molecules for anti-inflammatory inhibitory activity

Current Botany ◽

10.25081/cb.2021.v12.6583 ◽

2021 ◽

pp. 22-27

Author(s):

L. Thamaraiselvi ◽

T. Selvankumar ◽

E.G. Wesely ◽

N. Vinod Kumar

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

In Silico ◽

Novel Drugs ◽

In Silico Study ◽

Low Toxicity ◽

Cox 2 ◽

Anti Inflammatory ◽

In Silico Molecular Docking ◽

Oxide Synthase

Herbs are essential resources for drug discovery. However, numerous challenges stand in front of the scientific community to discover novel drugs from herbs. To explore the validation behind the precious knowledge of traditional medicine, we focused on achieving virtual screening to detect the potential medicines from the herbs. Five bioactive compounds from known anti-inflammatory medicinal plants were examined through molecular docking against cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS), using AutoDock 4.2. The docking of selected ligands with COX-2 showed the binding energy varying from -6.15 Kcal/mol to ‑11.24 Kcal/mol. The docking energies of identified ligands with iNOS were generated ranges from -3.85kcal/mol to -6.99 kcal/mol. Among the tested ligands, it was noted that 6 urs-12-en-24-oic acid showed the best binding energy than other compounds with the lowest binding energy and highest binding affinity with both anti-inflammatory target proteins COX-2 and iNOS. The in silico study validates the potential phytochemical compound of the medicinal herb that contribute to anti-inflammatory activity with low toxicity and minimal side effects.

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In silico study of COX-2 on indomethacin and diclofenac as nonsteroidal anti-inflammatory drugs (NSAIDs)

Farmasains Jurnal Farmasi dan Ilmu Kesehatan ◽

10.22219/farmasains.v4i1.7767 ◽

2019 ◽

Vol 4 (1) ◽

pp. 31

Author(s):

Janatun Na'imah

Keyword(s):

Amino Acids ◽

In Silico ◽

3D Structure ◽

Steric Interaction ◽

A Value ◽

Docking Method ◽

In Silico Study ◽

Inflammatory Drugs ◽

Cox 2 ◽

G Value

Cyclooxygenase is an enzyme that plays a role in the formation of prostaglandins, which can cause inflammation and pain when overexpressed. This study aims to determine the interaction between COX-2 macromolecules (receptors) with their ligands, namely indomethacin and diclofenac in silico using the Molecular Docking method. The COX-2 receptor was downloaded in the form of a 3D structure from the RCSB GDP with code 5F19. Diclofenac Ligand and Indomethacin were downloaded in the form of a 3D structure from the RCSB GDP with 4ZBQ code and 4IK7 code. The results showed that the interaction between COX-2 and indomethacin was the interaction of hydrogen, which linked indomethacin with amino acid Leu531 and steric interactions between indomethacin and amino acids Trp387, Tyr385, Tyr355, Leu352, and Val523. The interaction of [COX-2 – Indomethacin] produces a value of ∆G of -103.136 kcal/mol, and the value of RMSD is 1.244 Å. Whereas, the interaction that occurs in COX-2 with diclofenac is the steric interaction that happens between diclofenac with amino acids Leu390, Trp387, Gln203, His388, His207, and Thr206. The interaction parameter between [COX-2-Diclofenac] obtained ∆G value of -7.843 kcal/mol and an RMSD value of 2.07851 Å.

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