scholarly journals Kinase Inhibitors Can Inhibit SARS-CoV-2 Mpro: A Theoretical Study

2020 ◽  
Author(s):  
BN Acharya
Keyword(s):  
Kinase Inhibitors ◽  
Theoretical Study ◽  
3D Qsar ◽  
Qsar Model ◽  
Randomization Test ◽  
Pharmacophore Modeling ◽  
Ligand Docking ◽  
Receptor Ligand ◽  
Test Set ◽  
Approved Drugs

This study describes screening of DrugBank library for approved drugs by pharmacophore modeling and receptor-ligand docking. A 3D-QSAR model was generated on the<br>inhibition constants (Ki AutoDock ) determined by AutoDock. This 3D-QSAR model was statistically validated by Fischer’s randomization test and further evaluated by a test set<br>comprising 75 molecules. Ki AutoDock values of 49 molecules were predicted correctly by the 3D-QSAR model. The validated 3D-QSAR model was used for screening of DrugBank library for approved molecules to identify potential molecules against novel SARS corona virus-2 (SARS-CoV-2). Ten out of 40 the shortlisted molecules were kinase inhibitors.

scholarly journals Kinase Inhibitors Can Inhibit SARS-CoV-2 Mpro: A Theoretical Study

2020 ◽  
Author(s):  
BN Acharya
Keyword(s):  
Kinase Inhibitors ◽  
Theoretical Study ◽  
3D Qsar ◽  
Qsar Model ◽  
Randomization Test ◽  
Pharmacophore Modeling ◽  
Ligand Docking ◽  
Receptor Ligand ◽  
Test Set ◽  
Approved Drugs

This study describes screening of DrugBank library for approved drugs by pharmacophore modeling and receptor-ligand docking. A 3D-QSAR model was generated on the<br>inhibition constants (Ki AutoDock ) determined by AutoDock. This 3D-QSAR model was statistically validated by Fischer’s randomization test and further evaluated by a test set<br>comprising 75 molecules. Ki AutoDock values of 49 molecules were predicted correctly by the 3D-QSAR model. The validated 3D-QSAR model was used for screening of DrugBank library for approved molecules to identify potential molecules against novel SARS corona virus-2 (SARS-CoV-2). Ten out of 40 the shortlisted molecules were kinase inhibitors.

3D QSAR Pharmacophore Modeling for c-Met Kinase Inhibitors

2012 ◽  
Vol 8 (6) ◽  
pp. 1117-1125
Author(s):  
Dandan Huang ◽  
Xiaoyun Zhu ◽  
Chunlei Tang ◽  
Yicheng Mei ◽  
Wei Chen ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
3D Qsar ◽  
Pharmacophore Modeling

3D-QSAR and Pharmacophore modeling of 3,5-disubstituted indole derivatives as Pim kinase inhibitors

2020 ◽  
Vol 31 (5) ◽  
pp. 1675-1690
Author(s):  
Bhushan D. Varpe ◽  
Shailaja B. Jadhav ◽  
Bandoo C. Chatale ◽  
Anil S. Mali ◽  
Shravan Y. Jadhav ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
3D Qsar ◽  
Pharmacophore Modeling ◽  
Indole Derivatives

scholarly journals COMBINATORIAL PHARMACOPHORE MODELING AND ATOM BASED 3D QSAR STUDIES OF BENZOTHIADIAZINES AS HCV-NS5B INHIBITORS

2018 ◽  
Vol 10 (3) ◽  
pp. 43
Author(s):  
Prasanthi Polamreddy ◽  
Vinita Vishwakarma ◽  
Manoj Kumar Mahto
Keyword(s):  
Virtual Screening ◽  
Correlation Coefficient ◽  
Current Model ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Qsar Model ◽  
Pharmacophore Modeling ◽  
Structural Protein ◽  
Pearson's R ◽  
Pearson’S R

Objective: The objective of the current study was to elucidate the 3D pharmacophoric features of benzothiadiazine derivatives that are crucial for inhibiting Hepatitis C virus (HCV) Non-structural protein 5B (NS5B) and quantifying the features by building an atom based 3D quantitative structure-activity relationship (3D QSAR) model.Methods: Generation of QSAR model was carried out using PHASE 3.3.Results: A five-point pharmacophore model with two hydrogen bond acceptors, one negative ionization potential and two aromatic rings (AANRR) was found to be common among a maximum number of benzothiadiazine based NS5B inhibitors. A statistically significant 3D QSAR model was obtained from AANRR.6 which had correlation-coefficient (R2) value of 0.924, cross-validated correlation-coefficient (Q2) of 0.774, high Fisher ratio of 138 and low root mean square standard error (RMSE=0.29). There is another parameter, Pearson’s R, its value emphasizes correlation between predicted and observed activities of the test set. For the current model, Pearson’s R-value is 0.90, hence underlining the good quality of the model. The present study suggests that nitrogen atom of benzothiadiazine sulfamide ring, oxyacetamide group attached to C7 carbon of benzothiadiazine and sulfonamide oxygens are crucial for NS5B inhibitory activity. Prediction of activities of hit drugs generated in earlier research suggests that Aprepitant (Phase predicted activity: 6.9) could be a potential NS5B inhibitor.Conclusion: This 3D QSAR model developed was statistically good and can be used to predict the activities of newly designed NS5B inhibitors and virtual screening as well. Predict the activities of newly designed NS5B inhibitors and virtual screening as well.

scholarly journals Amodiaquine as COVID-19 Mpro Inhibitor: A Theoretical Study

2020 ◽  
Author(s):  
bnacharya Acharya
Keyword(s):  
Molecular Docking ◽  
Theoretical Study ◽  
Pharmacophore Modeling ◽  
World Health ◽  
Clinical Tests ◽  
Therapeutic Approaches ◽  
Global Pandemic ◽  
Screening And Identification ◽  
Health Organization ◽  
Approved Drugs

<div> <div> <div> <p>COVID-19 is caused by severe respiratory syndrome –coronavirus 2 (SARS CoV-2). This has been declared as a global pandemic by World Health Organization (WHO). Currently only supportive care is available for treatment of patients. However availability of direct therapeutic approaches would greatly benefit the patient care and reduce death among COVID- 19 patients. Repurposing of approved drugs against COVID-19 would be a faster method to identify direct therapeutics against COVID-19. This study describes screening and identification of Amodiaquine a known antimalarial as COVID-19 Mpro inhibitor by pharmacophore modeling and molecular docking. Amodiaquine may be repurposed as COVID-19 drug after thorough clinical tests. </p> </div> </div> </div>

scholarly journals VIRTUAL SCREENING, PHARMACOPHORE MODELING, AND QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES ON HISTAMINE 4 RECEPTOR

2017 ◽  
Vol 10 (12) ◽  
pp. 150
Author(s):  
Shobana Sugumar
Keyword(s):  
Virtual Screening ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Pharmacophore Modeling ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Hydrogen Bond Acceptor ◽  
Structure Activity

  Objective: To find out novel inhibitors for histamine 4 receptor (H4R), the target for various allergic and inflammatory pathophysiological conditions.Methods: Homology modeling of H4R was performed using easy modeler and validated using structure analysis and verification server, and with the modeled structure, virtual screening, pharmacophore modeling, and quantitative structure activity relationship (QSAR) studies were performed using the Schrodinger 9.3 software.Results: Among all the synthetic and natural ligands, hesperidin, vitexin, and diosmin were found to have the highest dock score, and with that, a five-point pharmacophore model was developed consisting of two hydrogen bond acceptor and three ring atoms, and the pharmacophore hypothesis yielded a statistically significant three-dimensional QSAR (3D-QSAR) model with a correlation coefficient of r2=0.8962 as well as good predictive power.Conclusion: The pharmacophore-based 3D-QSAR model generated from natural antihistamines can provide intricate structural knowledge about a new class of anti-allergic and anti-inflammatory drug research.

3D QSAR Pharmacophore Modeling for c-Met Kinase Inhibitors

2012 ◽  
Vol 8 (6) ◽  
pp. 1117-1125
Author(s):  
Dandan Huang ◽  
Xiaoyun Zhu ◽  
Chunlei Tang ◽  
Yicheng Mei ◽  
Wei Chen ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
3D Qsar ◽  
Pharmacophore Modeling

scholarly journals Docking and 3D QSAR Studies on p38α MAP Kinase Inhibitors

2011 ◽  
Vol 8 (4) ◽  
pp. 1596-1605
Author(s):  
Mohan Babu Jatavath ◽  
Sree Kanth Sivan ◽  
Yamini Lingala ◽  
Vijjulatha Manga
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Chemotherapeutic Agents ◽  
Field Analysis ◽  
Qsar Studies

The p38 signaling cascade has emerged as an attractive target for the design of novel chemotherapeutic agents for the treatment of inflammatory diseases. Three dimensional quantitative structure- activity relationship (3D- QSAR) studies were performed on a series of 25, 2-aminothiazole analogs as inhibitors of p38α mitogen activated protein (MAP) kinase. The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. The 3D-QSAR model showed very good statistical results namely q2, r2and r2predvalues for both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models & docking results provided the most significant correlation of steric, electrostatic, hydrophobic,H-bond donor,H-bond acceptor fields with biological activities and the provided values were in good agreement with the experimental results. The information rendered from molecular modeling studies gave valuable clues to optimize the lead and design new potential inhibitors.

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