Unveiling the Inhibitory Potentials of Peptidomimetic Azanitriles and Pyridyl Esters towards SARS-CoV-2Main Protease: A MolecularModelling Investigation

Simple item page
dc.contributor.authorMushebenge, Aganze G
dc.contributor.authorUgbaja, Samuel C
dc.contributor.authorMtambo, Sphamandla E
dc.contributor.authorOdugbemi, Adeshina I
dc.date.accessioned2023-04-14T12:48:17Z
dc.date.available2023-04-14T12:48:17Z
dc.date.issued2023
dc.description.abstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19, which was declared a global pandemic in March 2020 by the World Health Organization (WHO). Since SARS-CoV-2 main protease plays an essential role in the virus’s life cycle, the design of small drug molecules with lower molecular weight has been a promising development targeting its inhibition. Herein, we evaluated the novel peptidomimetic azatripeptide and azatetrapeptide nitriles against SARS-CoV-2 main protease. We employed molecular dynamics (MD) simulations to elucidate the selected compounds’ binding free energy profiles against SARS-CoV-2 and further unveil the residues responsible for the drug-binding properties. Compound 8 exhibited the highest binding free energy of 􀀀49.37 0.15 kcal/mol, followed by compound 7 (􀀀39.83 0.19 kcal/mol), while compound 17 showed the lowest binding free energy (􀀀23.54 0.19 kcal/mol). In addition, the absorption, distribution, metabolism, and excretion (ADME) assessment was performed and revealed that only compound 17 met the drug-likeness parameters and exhibited high pharmacokinetics to inhibit CYP1A2, CYP2C19, and CYP2C9 with better absorption potential and blood-brain barrier permeability (BBB) index. The additional intermolecular evaluations suggested compound 8 as a promising drug candidate for inhibiting SARS-CoV-2 Mpro. The substitution of isopropane in compound 7 with an aromatic benzene ring in compound 8 significantly enhanced the drug’s ability to bind better at the active site of the SARS-CoV-2 Mpro.en_US
dc.identifier.citationMushebenge, A.G, et al . (2023). Unveiling the inhibitory potentials of peptidomimetic azanitriles and pyridyl esters towards SARS-CoV-2 main protease: A molecular modelling investigation. Molecules, 28(6) doi:10.3390/molecules28062641en_US
dc.identifier.urihttps://doi.org/10.3390/molecules28062641
dc.identifier.urihttp://hdl.handle.net/10566/8808
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.subjectSARS-CoV-2 main proteaseen_US
dc.subjectADMEen_US
dc.subjectBinding free energyen_US
dc.subjectMolecular dynamics simulationsen_US
dc.titleUnveiling the Inhibitory Potentials of Peptidomimetic Azanitriles and Pyridyl Esters towards SARS-CoV-2Main Protease: A MolecularModelling Investigationen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
mushebenga-et-al_unveiling-the-Inhibitory-Potentials-of-Peptidomimetic-Azanitriles-and-Pyridyl-Esters-towards-SARSCoV2-_2023.pdf
Size:
4.81 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research Articles (Medical Bioscience)