Molecular docking studies, molecular dynamics and ADME/tox reveal therapeutic potentials of STOCK1N-69160 against papain-like protease of SARS-CoV-2

Elekofehinti, Olusola Olalekan; Iwaloye, Opeyemi; Josiah, Sunday Solomon; Lawal, Akeem O.; Akinjiyan, Moses Orimoloye; Ariyo, Esther Opeyemi

doi:10.1007/s11030-020-10151-w

Cited by 56 publications

(24 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The docking protocol was validated by computing the relative binding free energies of the docked protein-ligand complex [ 74 ]. Prime MM-GBSA calculates various energy components of the protein, ligand and protein-ligand complex.…”

Section: Resultsmentioning

confidence: 99%

Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2

Prabhu

Rajamanikandan

Sureshan

et al. 2021

Journal of Molecular Graphics and Modelling

View full text Add to dashboard Cite

COVID-19 pandemic causative SARS-CoV-2 coronavirus is still rapid in progression and transmission even after a year. Understanding the viral transmission and impeding the replication process within human cells are considered as the vital point to control and overcome COVID-19 infection. Non-structural Protein 1, one among the proteins initially produced upon viral entry into human cells, instantly binds with the human ribosome and inhibit the host translation process by preventing the mRNA attachment. However, the formation of NSP1 bound Ribosome complex does not affect the viral replication process. NSP1 plays an indispensable role in modulating the host gene expression and completely steals the host cellular machinery. The full-length structure of NSP1 is essential for the activity in the host cell and importantly the loop connecting N and C- terminal domains are reported to play a role in ribosome binding. Due to the unavailability of the experimentally determined full-length structure of NSP1, we have modelled the complete structure using comparative modelling and the stability and conformational behaviour of the modelled structure was evaluated through molecular dynamics simulation. Interestingly, the present study reveals the significance of the inter motif loop to serves as a potential binding site for drug discovery experiments. Further, we have screened the phytochemicals from medicinal plant sources since they were used for several hundred years that minimizes the traditional drug development time. Among the 5638 phytochemicals screened against the functionally associated binding site of NSP1, the best five phytochemicals shown high docking score of -9.63 to -8.75 kcal/mol were further evaluated through molecular dynamics simulations to understand the binding affinity and stability of the complex. Prime MM-GBSA analysis gave the relative binding free energies for the top five compounds (dihydromyricetin, 10-demethylcephaeline, dihydroquercetin, pseudolycorine and tricetin) in the range of -45.17 kcal/mol to -37.23 kcal/mol, indicating its binding efficacy in the predicted binding site of NSP1. The density functional theory calculations were performed for the selected five phytochemicals to determine the complex stability and chemical reactivity. Thus, the identified phytochemicals could further be used as effective anti-viral agents to overcome COVID-19 and as well as several other viral infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2

Prabhu

Rajamanikandan

Sureshan

et al. 2021

Journal of Molecular Graphics and Modelling

View full text Add to dashboard Cite

show abstract

“… 31 It predicts the binding model and energy of compounds with the active pose of target proteins. 32 The compounds in this study demonstrated varying degree of binding affinities for the targets as shown in Table 4 . The binding affinity of drimenin (−9.1 kcal/mol) for α-synuclein was observed to be higher than the standard ligand (donepezil: −8.7 kcal/mol).…”

Section: Discussionmentioning

confidence: 95%

Identification of Terpenoids From Abrus precatorius Against Parkinson’s Disease Proteins Using In Silico Approach

Omoboyowa

Balogun

Omomule

et al. 2021

Bioinform Biol Insights

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second major neuro-degenrative disorder that causes morbidity and mortality among older populations. Terpenoids were reported as potential neuro-protective agents. Therefore, this study seeks to unlock the inhibitory potential of terpenoids from Abrus precatorius seeds against proteins involve in PD pathogenesis. In this study, in silico molecular docking of 5 terpenoids derived from high-performance liquid chromatography (HPLC) analysis of A. precatorius seeds against α-synuclein, catechol-o-methyltransferase, and monoamine oxidase B which are markers of PD was performed using Autodock vina. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) of the hits were done using Swiss ADME predictor and molecular dynamic (MD) simulation of the hit-protein complex was performed using Desmond Schrodinger software. Five out of 6 compounds satisfied the ADME/Tox parameters and showed varying degrees of binding affinities with selected proteins. Drimenin-α-synuclein complex showed the lowest binding energy of −9.1 kcal/mol followed by interaction with key amino acid residues necessary for α-synuclein inhibition. The selection of this complex was justified by its stability in MD simulation conducted for 10 ns and exhibited stable interaction in terms of root mean square deviation (RMSD) and root mean square deviation error fluctuation (RMSF) values.

show abstract

“…The reliability of the molecular docking result was determined by estimating the binding free energy through the Prime MM-GBSA module of Maestro. This approach is one of the most reliable methods of validating docking results as it helps to determine the stability of the receptor-ligand complex 41,42 . This denotes that a favorable binding free energy correlate to a reliable output from molecular docking study.…”

Section: Discussionmentioning

confidence: 99%

Identification of Possible Inhibitors of SARS-CoV-2 Main Protease From Some Bioactive Compounds of Artemisia Annua: An in Silico Approach

Johnson

Adegboyega

Ojo

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses including the coronavirus is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2, that is currently ravaging the world. It is therefore necessary to identify the bioactive compounds of the plants that are responsible for this activity, for the purpose of designing drugs against SARS-CoV-2. In this study, we employed in silico techniques comprising of molecular docking, binding free energy calculations, pharmacophore modelling as well as druglikeness, pharmacokinetics and toxicity predictions, to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, Isokaempferide, Kaempferol, Quercimeritrin, Apigenin, Penduletin, Isoquercitrin, Astragalin, Luteolin-7-glucoside and Isorhamnetin were ranked highest; with docking scores ranging from -7.84 to -7.15 kcal/mol compared with -6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide and Kaempferol, like the standard ligand interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. These compounds also possess acceptable druglike properties and safety profile. Hence, they could be considered for experimental studies and further development into drugs against SARS-CoV-2.

show abstract

Molecular docking studies, molecular dynamics and ADME/tox reveal therapeutic potentials of STOCK1N-69160 against papain-like protease of SARS-CoV-2

Cited by 56 publications

References 49 publications

Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2

Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2

Identification of Terpenoids From Abrus precatorius Against Parkinson’s Disease Proteins Using In Silico Approach

Identification of Possible Inhibitors of SARS-CoV-2 Main Protease From Some Bioactive Compounds of Artemisia Annua: An in Silico Approach

Contact Info

Product

Resources

About