dc.contributor.author | Mushebenge, Aganze G | |
dc.contributor.author | Ugbaja, Samuel C | |
dc.contributor.author | Mtambo, Sphamandla E | |
dc.contributor.author | Odugbemi, Adeshina I | |
dc.date.accessioned | 2023-04-14T12:48:17Z | |
dc.date.available | 2023-04-14T12:48:17Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Mushebenge, 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/molecules28062641 | en_US |
dc.identifier.uri | https://doi.org/10.3390/molecules28062641 | |
dc.identifier.uri | http://hdl.handle.net/10566/8808 | |
dc.description.abstract | The 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.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.subject | SARS-CoV-2 main protease | en_US |
dc.subject | ADME | en_US |
dc.subject | Binding free energy | en_US |
dc.subject | Molecular dynamics simulations | en_US |
dc.title | Unveiling the Inhibitory Potentials of Peptidomimetic Azanitriles and Pyridyl Esters towards SARS-CoV-2Main Protease: A MolecularModelling Investigation | en_US |
dc.type | Article | en_US |