Discovery of anti-MERS-CoV small covalent inhibitors through pharmacophore modeling, covalent docking and molecular dynamics simulation

Alamri, Mubarak A.; Qamar, Muhammad Tahir ul; Afzal, Obaid; Alabbas, Alhumaidi B.; Riadi, Yassine; Alqahtani, Safar M.

doi:10.1016/j.molliq.2021.115699

Cited by 38 publications

(25 citation statements)

References 70 publications

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“…Molecular dynamic simulation (100 ns) was performed using Gromacs 2018 (GNU Lesser General Public License, Boston, USA) ( Alamri et al, 2021 ). The CHARMM36 force field was used in all simulation.…”

Section: Methodsmentioning

confidence: 99%

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Zhao

et al. 2022

LWT

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COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (M pro ), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were predicted using various online tools. The molecular interactions between M pro and the peptides were studied using molecular docking and molecular dynamic simulation. The results demonstrated that peptide GSRY was predicted to have better physicochemical properties, and the value of ‘-C DOCKER interaction energy’ between peptide GSRY and M pro was 80.8505 kcal/mol. The interaction between the peptide GSRY and the native ligand N3 co-crystallized with M pro had overlapped amino acids, i.e., HIS163, GlY143, GLU166, GLN189 and MET165. Molecular dynamic simulation revealed that M pro /GSRY complexes were stable. Collectively, the peptide GSRY may be a potential candidate drug against M pro of SARS-CoV-2.

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Section: Methodsmentioning

confidence: 99%

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Zhao

et al. 2022

LWT

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“…MD simulations were conducted using the AMBER20 suite of molecular dynamics program with the force filed FF14SB [ 27 , 28 ]. AMBER force field (GAFF) using the Antechamber program was used to generate force-field parameters for the ligand molecules [ 29 , 30 ]. The studied systems were then solvated by immersing each complex in a cubic box of TIP3P water molecules with a 10 Å solute-wall distance.…”

Section: Methodsmentioning

confidence: 99%

Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide‐P of Momordica charantia

Arif

Ahmad

Mustafa

et al. 2021

BioMed Research International

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Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body’s inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski’s rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

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“…Hou T et al described that to calculate the relative

, MM-GBSA is better in terms of result accuracy than MM-PBSA ( Gohlke et al, 2004 ; Hou et al, 2011 ; JyrkkäRinne et al, 2012 ). This approach has been extensively employed in protein–protein interaction and protein–ligand binding studies ( Alamri et al, 2021 ; Tahir ul Qamar et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Discovery of Novel Inhibitors From Medicinal Plants for V-Domain Ig Suppressor of T-Cell Activation

Muneer

Ahmad

Naz

et al. 2021

Front. Mol. Biosci.

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V-domain Ig suppressor of T cell activation (VISTA) is an immune checkpoint and is a type I transmembrane protein. VISTA is linked to immunotherapy resistance, and it is a potential immune therapeutic target, especially for triple-negative breast cancer. It expresses at a high concentration in regulatory T cells and myeloid-derived suppressor cells, and its functional blockade is found to delay tumor growth. A useful medicinal plant database for drug designing (MPD3), which is a collection of phytochemicals from diverse plant families, was employed in virtual screening against VISTA to prioritize natural inhibitors against VISTA. Three compounds, Paratocarpin K (PubChem ID: 14187087), 3-(1H-Indol-3-yl)-2-(trimethylazaniumyl)propanoate (PubChem ID: 3861164), and 2-[(5-Benzyl-4-ethyl-1,2,4-triazol-3-yl)sulfanylmethyl]-5-methyl-1,3,4-oxadiazole (PubChem ID: 6494266), having binding energies stronger than −6 kcal/mol were found to have two common hydrogen bond interactions with VISTA active site residues: Arg54 and Arg127. The dynamics of the compound–VISTA complexes were further explored to infer binding stability of the systems. Results revealed that the compound 14187087 and 6494266 systems are highly stable with an average RMSD of 1.31 Å. Further affirmation on the results was achieved by running MM-GBSA on the MD simulation trajectories, which re-ranked 14187087 as the top-binder with a net binding energy value of −33.33 kcal/mol. In conclusion, the present study successfully predicted natural compounds that have the potential to block the function of VISTA and therefore can be utilized further in experimental studies to validate their real anti-VISTA activity.

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Discovery of anti-MERS-CoV small covalent inhibitors through pharmacophore modeling, covalent docking and molecular dynamics simulation

Cited by 38 publications

References 70 publications

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide‐P of Momordica charantia

Discovery of Novel Inhibitors From Medicinal Plants for V-Domain Ig Suppressor of T-Cell Activation

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