Target-based drug discovery, ADMET profiling and bioactivity studies of antibiotics as potential inhibitors of SARS-CoV-2 main protease (Mpro)

Abdul-Hammed, Misbaudeen; Adedotun, Ibrahim Olaide; Falade, Victoria Adeola; Adepoju, Adewusi John; Olasupo, Sabitu Babatunde; Akinboade, Modinat Wuraola

doi:10.1007/s13337-021-00717-z

Cited by 43 publications

(15 citation statements)

References 59 publications

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“…We have also established additional ligand efficiency scores to shed more light on the bioactivity of 1 and 2 towards the applied SARS-CoV-2 proteins. As such, for all complexes of 1 and 2 with the studied proteins, we have calculated inhibition constant ( K i ), miLogP, ligand efficiency (LE), ligand efficiency_scale (LE_Scale), fit quality (FQ) and ligand-efficiency-dependent lipophilicity (LELP) [ 38 , 39 , 40 , 41 , 42 , 43 ] ( Table 2 ). Furthermore, for comparison we have also calculated the same ligand efficiency scores for complexes of the studied proteins with initial ligands ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, for comparison we have also calculated the same ligand efficiency scores for complexes of the studied proteins with initial ligands ( Table 2 ). Notably, the K i value must be as low as possible for a more efficient inhibition and should fall in the μM range for a compound to be considered as a Hit, and >10 nM for a drug [ 42 ]. Furthermore, for a compound to be considered as a Hit the LE, FQ and LELP parameters are recommended as ≥0.3, ≥0.8 and from −10 to 10, respectively [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

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Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

2023

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We report two complexes [Cu(LI)2] (1) and [Cu(LII)2] (2) (HLI = N-cyclohexyl-3-methoxysalicylideneimine, HLII = N-cyclohexyl-3-ethoxysalicylideneimine). The ligands in both complexes are trans-1,5-N,O-coordinated, yielding a square planar CuN2O2 coordination core. The molecule of 1 is planar with two cyclohexyl groups oriented to the opposite sites of the planar part of a molecule, while the molecule of 2 is significantly bent with two cyclohexyl groups oriented to the same convex site of a molecule. It was established that both complexes in MeOH absorb in the UV region due to intraligand transitions and LMCT. Furthermore, the UV-vis spectra of both complexes revealed two low intense shoulders in the visible region at about 460 and 520 nm, which were attributed to d–d transitions. Both complexes were predicted to belong to a fourth class of toxicity with the negative BBB property and positive gastrointestinal absorption property. According to the molecular docking analysis results, both complexes are active against all the applied SARS-CoV-2 proteins with the best binding affinity with Nsp 14 (N7-MTase), PLpro and Mpro. The obtained docking scores of complexes are either comparable to or even higher than those of the initial ligands. Complex 1 was found to be more efficient upon interaction with the applied proteins in comparison to complex 2. Ligand efficiency scores for the initial ligands, 1 and 2 were also revealed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

2023

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“…SARS-CoV-2 M pro is the most propitious therapeutic target for the development of COVID-19 inhibitors and has been the focus of several studies [ 7 – 11 ]. The structure of M pro suggests that it is a dimer that comprises six-stranded antiparallel β-barrels, with a substrate-binding site between them, as well as cluster of five helical complexes [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Bioprospecting phytochemicals of Rosmarinus officinalis L. for targeting SARS-CoV-2 main protease (Mpro): a computational study

et al. 2023

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Context The persistent spread of highly contagious COVID-19 disease is one of the deadliest occurrences in the history of mankind. Despite the distribution of numerous efficacious vaccines and their extensive usage, the perpetual effectiveness of immunization is being catechized. Therefore, discovering an alternative therapy to control and prevent COVID-19 infections has become a top priority. The main protease (M pro ) plays a key role in viral replication, making it an intriguing pharmacological target for SARS-CoV-2. Methods In this context, virtual screening of thirteen bioactive polyphenols and terpenoids of Rosmarinus officinalis L. was performed using several computational modules including molecular docking, ADMET, drug-likeness characteristics, and molecular dynamic simulation to predict the potential inhibitors against SARS-CoV-2 M pro (PDB: 6LU7). The results suggest that apigenin, betulinic acid, luteolin, carnosol, and rosmarinic acid may emerge as potential inhibitors of SARS-CoV-2 with acceptable drug-likeness, pharmacokinetics, ADMET characteristics, and binding interactions comparable with remdesivir and favipiravir. These findings imply that some of the active components of Rosmarinus officinalis L. can serve as an effective antiviral source for the development of therapeutics for SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s00894-023-05569-6.

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“…Phytochemicals derived from papayas such as flavonoids, terpenoids, tannins, and phenols have been found to have anti-psoriatic and antiinflammatory effects associated with psoriasis [15]. This study aims at investigating the anti-psoriatic and antiinflammatory potential phytochemicals found in the Papaya plant against two psoriasis targeted enzymes; JAK1 (PDB ID: 6N7B) and TNFα (PDB ID: 2AZ5) through molecular docking coupled with ADMET studies, pharmacokinetic evaluation, drug likeliness among other analyses at a therapeutic dose as used previously in the study on enzyme inhibitors of SARS-COV2 main protease [16,17] and human tyrosinase-related protein [18].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Bioactive Compounds from Carica papaya in the Management of Psoriasis using Computational Techniques

Abdul-Hammed

Adedotun

Afolabi

et al. 2023

J. Nig. Soc. Phys. Sci.

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Psoriasis is a persistent and mysterious autoimmune skin condition that affects 2-3% of the world’s population. Currently, topical therapies, light therapy, and systemic drugs are the three main forms of treatment used to lessen inflammation and skin irritation/itching. However, all these treatments are only used to manage the disease each time it surfaces. Therefore, the main target of this work is to search for a safer and more effective remedy for psoriasis from the reservoir of phytochemicals present in Carica papaya via in silico studies due to its anti-psoriatic and anti-inflammatory properties. Reported phytochemicals isolated from Carica papaya were subjected to computational simulations using the PyRx docking tool and were docked against Janus Kinase 1 (JAK1) and Tumor necrosis factor \aplha (TNF\aplha) target receptors. The results obtained were visualized using PyMol, and Biovia 2019. Analysis of the results identified both Chlorogenic acid and Coumaroylquinic-acid with docking scores (-8.6 kcal/mol and -7.9 kcal/mol) respectively as potential inhibitors for the JAK1 receptor. The identified compounds also possessed excellent ADMET, drug-likeness, bioactivity, and activity spectra for substances (PASS) prediction properties. Their binding mode and the molecular interactions with the targets also affirmed their potency. In comparison with the standards (Methotrexate and Cyclosporine), Chlorogenic acid and Coumaroylquinic-acid have better ADMET properties, binding affinities, drug-likeness, PASS properties, bioactivities, oral bioavailability, binding mechanism, and interactions with the active site of the target receptor and are hereby recommended for further analysis towards the development of a new therapeutic agent for psoriasis treatment and management.

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Target-based drug discovery, ADMET profiling and bioactivity studies of antibiotics as potential inhibitors of SARS-CoV-2 main protease (Mpro)

Cited by 43 publications

References 59 publications

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

Bioprospecting phytochemicals of Rosmarinus officinalis L. for targeting SARS-CoV-2 main protease (Mpro): a computational study

Analysis of the Bioactive Compounds from Carica papaya in the Management of Psoriasis using Computational Techniques

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