Screening and Structure-Activity Relationship of Potential Compounds against Proposed Targets of COVID-19 Infection

2021 ◽  
Vol 18 ◽  
Author(s):  
Majid Ali ◽  
Asma Zaidi ◽  
Umar Farooq ◽  
Syed Majid Bukhari
Keyword(s):  
Molecular Docking ◽  
Chemokine Receptors ◽  
Acetylcholine Receptors ◽  
Viral Infections ◽  
Close Relation ◽  
Docking Studies ◽  
Muscarinic Acetylcholine Receptors ◽  
Molecular Docking Studies ◽  
Dipeptidyl Peptidase 4 ◽  
Relationship Of

Background: With reference to COVID-19 pandemic prevailing across the globe, chloroquine and hyrdoxycholoroquine were reported as effective against the disease to some extent. This effectiveness can be attributed to the glycosylation interruption of Angiotensin-converting enzyme 2 (ACE2) receptor which is a known target for SARS-CoV-2 entery. On the other hand, studies suggest that inhibition of ACE2 can prove to be lethal in certain cases thereby causing cardiovascular disorders, specially in patients already suffering from heart related diseases. Methods: In this study, most probable targets (other than ACE2) have been proposed for the treatment of COVID-19 infection by taking chloroquine and hydroxychloroquine as reference drugs. To achieve this objective, SwissTargetPrediction and PASSonline tools were used. Known drugs against each target possessing close relation to either viral infections or lung disorders were assessed from DrugBank database and simultaneous efficacy of these drugs towards other proposed targets were analyzed. By taking most effective drugs as reference, similar compounds were screened from ChEMBL library by using SwissSimilarity tool. Finally, molecular docking studies were performed through MOE software by using screened compounds against proposed targets. Results: Four most probable targets have been proposed including chemokine receptors (CCRs), dipeptidyl peptidase 4 (DPP4), muscarinic acetylcholine receptors (CHRMs) and histamine N-methyltransferase (HNMT). Furthermore, it has been evaluated that Quinacrine and vildagliptin are effective against most of the proposed targets. Taking vildagliptin and quinacrine as reference drugs, eight other similar compounds effective against these targets have been screened from ChEMBL library. Molecular docking studies with CCR5, DPP4 and CHRM5 suggested that quinacrine and its analogue (ChEMBL1782742) as well as vildagliptin and its analogue (ChEMBL511785) are the most suitable compounds hitting these targets. Conclusions: It has been established that quinacrine, ChEMBL1782742, vildagliptin, ChEMBL511785, mavorixafor, atropine, and N-(2-aminoethyl)-1-aziridineethanamine can be considered as effective in descending order for the treatment of COVID-19 infection.

scholarly journals IN SILICO STUDIES ON FUNCTIONALIZED AZAGLYCINE DERIVATIVES CONTAINING 2, 4-THIAZOLIDINEDIONE SCAFFOLD ON MULTIPLE TARGETS

2017 ◽  
Vol 9 (8) ◽  
pp. 209 ◽  
Author(s):  
Arifa Begum ◽  
Shaheen Begum ◽  
Prasad Kvsrg ◽  
Bharathi K.
Keyword(s):  
Molecular Docking ◽  
Oral Bioavailability ◽  
In Silico ◽  
Viral Infections ◽  
Target Prediction ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Molecular Docking Studies ◽  
In Silico Studies ◽  
Glycine Derivative

Objective: The 2, 4-thiazolidinedione containing compounds could lead to most promising scaffolds with higher efficiency toward the targets recognized for its antidiabetic activity when combined with azaglycine moiety. The objective of the present work was to merge functionalized aza glycines with 2, 4-thiazolidinediones, perform in silico evaluation by molecular properties prediction and undertake the molecular docking studies with targets relevant to diabetes, bacterial and viral infections using Swiss Dock programme for unraveling the target identification which can be used for further designing.Methods: (i) In silico studies were performed using Molinspiration online tool, Swiss ADME website and Swiss Target Prediction websites to compute the physicochemical descriptors, oral bioavailability and brain penetration. (ii) Molecular docking studies were performed using Swiss Dock web service for enumeration of binding affinities and assess their biological potentiality.Results: The results predicted good drug likeness, solubility, permeability and oral bioavailability for the compounds. All the compounds showed good docking scores as compared to the reference drugs. The N-oleoyl functionalized aza glycine derivative demonstrated superior binding properties towards all the studied target reference proteins, suggesting its significance in pharmacological actions.Conclusion: The binding interactions observed in the molecular docking studies suggest good binding affinity of the oleoyl functionalized aza glycine derivative, indicating that this derivative would be a promising lead for further investigations of anti-viral, anti-inflammatory and anti-diabetic activities.

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

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