Skip to Main content Skip to Navigation
Journal articles

COVID-19: In silico identification of potent α-ketoamide inhibitors targeting the main protease of the SARS-CoV-2

Abstract : The COVID-19 has been creating a global crisis, causing countless deaths and unbearable panic. Despite the progress made in the development of the vaccine, there is an urge need for the discovery of antivirals that may better work at different stages of SARS-CoV-2 reproduction. The main protease (M pro) of the SARS-CoV-2 is a crucial therapeutic target due to its critical function in virus replication. The α-ketoamide derivatives represent an important class of inhibitors against the M pro of the SARS-CoV. While there is 99% sequence similarity between SARS-CoV and SARS-CoV-2 main proteases, anti-SARS-CoV compounds may have a huge demonstration's prospect of their effectiveness against the SARS-CoV-2. In this study, we applied various computational approaches to investigate the inhibition potency of novel designed α-ketoamide-based compounds. In this regard, a set of 21 α-ketoamides was employed to construct a QSAR model, using the genetic algorithm-multiple linear regression (GA-MLR), as well as a pharmacophore fit model. Based on the GA-MLR model, 713 new designed molecules were reduced to 150 promising hits, which were later subject to the established pharmacophore fit model. Among the 150 compounds, the best selected compounds (3 hits) with greater pharmacophore fit score were further studied via molecular docking, molecular dynamic simulations along with the Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Our approach revealed that the three hit compounds could serve as potential inhibitors against the SARS-CoV-2 M pro target.
Complete list of metadata

https://hal-normandie-univ.archives-ouvertes.fr/hal-03264711
Contributor : Didier Villemin Connect in order to contact the contributor
Submitted on : Friday, June 18, 2021 - 2:41:03 PM
Last modification on : Tuesday, October 19, 2021 - 11:34:15 PM
Long-term archiving on: : Sunday, September 19, 2021 - 6:46:13 PM

File

428h.pdf
Files produced by the author(s)

Identifiers

Citation

Mehdi Oubahmane, Ismail Hdoufane, Imane Bjij, Carola Jerves, Didier Villemin, et al.. COVID-19: In silico identification of potent α-ketoamide inhibitors targeting the main protease of the SARS-CoV-2. Journal of Molecular Structure, Elsevier, In press, ⟨10.1016/j.molstruc.2021.130897⟩. ⟨hal-03264711⟩

Share

Metrics

Record views

67

Files downloads

34