<i>In Silico</i>molecular docking and dynamic analysis of natural compounds against major non-structural proteins of SARS-COV-2

Rehman, Muneeb U.; Ali, Aarif; Ansar, Ruhban; Arafah, Azher; Imtiyaz, Zuha; Wani, Tanveer A.; Zargar, Seema; Ganie, Showkat Ahmad

doi:10.1080/07391102.2022.2139766

Cited by 20 publications

(4 citation statements)

References 74 publications

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“…In this study, ADMET properties were used to determine the pharmacokinetics of drugs in the body. The five parameters of Lipinski's rule were used to determine the drug-like properties of compounds, and these features are mostly important as they are related to dissolution and intestinal permeability [39,[53][54][55]. In our study, all the molecules followed Lipinski's rule except rutin, which has a molecular weight >500 g/mol, a number of hydrogen bond donors >5, and a number of acceptors >10.…”

Section: Discussionmentioning

confidence: 90%

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein

Ali,

Wani,

Malla

et al. 2023

Medicina

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Background and Objectives: Cyclooxygenase-2 (COX-2) is mostly linked to inflammation and has been validated as a molecular target for treating inflammatory diseases. The present study aimed to identify novel compounds that could inhibit COX-2, which is associated with various diseases including inflammation, and in such a scenario, plant-derived biomolecules have been considered as attractive candidates. Materials and Methods: In the present study, physiochemical properties and toxicity of natural compounds/drugs were determined by SWISSADME and ProTox-II. In the present study, the molecular docking binding features of saffron derivatives (crocetin, picrocrocin, quercetin, safranal, crocin, rutin, and dimethylcrocetin) against human COX-2 protein were assessed. Moreover, protein-protein interactions, topographic properties, gene enrichment analysis and molecular dynamics simulation were also determined. Results: The present study revealed that picrocrocin showed the highest binding affinity of −8.1 kcal/mol when docked against the COX-2 protein. PROCHECK analysis revealed that 90.3% of the protein residues were found in the most favored region. Compartmentalized Protein–Protein Interaction identified 90 interactions with an average interaction score of 0.62, and the highest localization score of 0.99 found in secretory pathways. The Computed Atlas of Surface Topography of Proteins was used to identify binding pockets and important residues that could serve as drug targets. Use of WEBnmα revealed protein dynamics by using normal mode analysis. Ligand and Receptor Dynamics used the Molecular Generalized Born Surface Area approach to determine the binding free energy of the protein. Gene enrichment analysis revealed that ovarian steroidogenesis, was the most significant enrichment pathway. Molecular dynamic simulations were executed for the best docked (COX-2-picrocrocin) complex, and the results displayed conformational alterations with more pronounced surface residue fluctuations in COX-2 with loss of the intra-protein hydrogen bonding network. The direct interaction of picrocrocin with various crucial amino-acid residues like GLN203, TYR385, HIS386 and 388, ASN382, and TRP387 causes modifications in these residues, which ultimately attenuates the activity of COX-2 protein. Conclusions: The present study revealed that picrocrocin was the most effective biomolecule and could be repurposed via computational approaches. However, various in vivo and in vitro observations are still needed.

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Section: Discussionmentioning

confidence: 90%

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein

Ali,

Wani,

Malla

et al. 2023

Medicina

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“…The physiochemical properties of phytocompounds were determined by ADMET analysis. The evaluation of drug-like properties are particularly important as they are associated with dissolution and intestinal permeability [ 60 , 61 , 62 ]. Bioactive compounds cannot be used as drug moieties if they fail in more than two rules, as mentioned by Lipinski [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

et al. 2023

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In glucose metabolism, the pentose phosphate pathway (PPP) is the major metabolic pathway that plays a crucial role in cancer growth and metastasis. Although it has been pointed out that blockade of the PPP is a promising approach against cancer, in the clinical setting, effective anti-PPP agents are still not available. Dysfunction of the G6PD enzyme in this pathway leads to cancer development as this enzyme possesses oncogenic activity. In the present study, an attempt was made to identify bioactive compounds that can be developed as potential G6PD inhibitors. In the present study, 11 natural compounds and a controlled drug were taken. The physicochemical and toxicity properties of the compounds were determined via ADMET and ProTox-II analysis. In the present study, the findings of docking studies revealed that staurosporine was the most effective compound with the highest binding energy of −9.2 kcal/mol when docked against G6PD. Homology modeling revealed that 97.56% of the residues were occupied in the Ramachandran-favored region. The modeled protein gave a quality Z-score of −10.13 by ProSA tool. iMODS server provided significant insights into the mobility, stability and flexibility of the G6PD protein that described the collective functional protein motion. In the present study, the physical and functional interactions between proteins were determined by STRING. CASTp server determined the topological and geometric properties of the G6PD protein. The findings of the present study revealed that staurosporine could be developed as a potential G6PD inhibitor; however, further in vivo and in vitro studies are needed for further validation of these results.

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“…In the drug discovery process, ADMET studies are particularly significant [40,41]. A compound must follow Lipinski's rule of five parameters before it can be developed as a drug moiety and if a substance fails in more than two parameters, it cannot be developed as a drug [42].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Computational Assessment of Acute Phase Proteins in Dairy Cows Affected with Subclinical Mastitis

Ali

Rehman

Mushtaq

et al. 2023

CIMB

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Subclinical mastitis (SCM) is a predominant form of mastitis wherein major visible signs of disease are absent. The present study aimed to determine acute phase proteins (APPs) like ferritin, C-reactive protein (CRP), and microalbumin (Malb) in 135 composite milk and serum samples of healthy (n = 25) and SCM (n = 110) cows. As bovine mastitis is an inflammatory disease, the present study also aimed at finding novel anti-inflammatory compounds from natural sources by repurposing approach using computational studies. The findings of the present study revealed substantial elevation (p < 0.001) in milk SCC and an increase in ferritin, CRP, and Malb (p < 0.001) in milk and sera of the SCM group as compared to healthy animals. Receiver operating characteristics of milk SCC, milk, and serum APPs unraveled statistically substantial alteration (p < 0.001). Further, SCC was correlated with milk APPs ferritin (r = 0.26 **, p < 0.002), CRP (r = 0.19 *, p < 0.02), and Malb (r = 0.21 *, p < 0.01). Additionally, milk SCC was correlated with serum ferritin (r = 0.28 **, p < 0.001), CRP (r = 0.16, p > 0.05), and Malb (r = 0.16, p > 0.05). The findings of molecular docking revealed that Chaetoglobosin U was the most effective molecule that showed the highest binding affinity (kcal/mol) of −10.1 and −8.5 against ferritin and albumin. The present study concluded that the estimation of cow-side tests, SCC, and APPs in milk/serum is suitable to detect SCM and screening herd community. Furthermore, Chaetoglobosin U could be developed as a promising anti-inflammatory inhibitor; however, further studies are required to validate these findings.

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In Silicomolecular docking and dynamic analysis of natural compounds against major non-structural proteins of SARS-COV-2

Cited by 20 publications

References 74 publications

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

Biochemical and Computational Assessment of Acute Phase Proteins in Dairy Cows Affected with Subclinical Mastitis

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