Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed as the causative virus of COVID-19 disease, which is currently a worldwide pandemic. Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is one of the most potent chemical compounds proposed to treat COVID-19 infection. We, therefore, performed virtual screening on FDA approved drugs that are similar to the efavirenz moiety. Subsequently, the compounds were subjected to screening by analyzing their drug-likeness, such as Lipinski's rule of five and ADMET properties. Molecular docking study revealed that Met165, His41, His163, and Phe140 were important interacting residues for COVID-19 main protease receptor-ligand interaction. Five top-ranked compounds, podophyllotoxin, oxacillin, lovastatin, simvastatin, and gefitinib, were selected by virtual screening and docking studies. The highest occupied molecular (HOMO) orbital, lowest unoccupied molecular orbital (LUMO) and energy gap values was calculated using density functional theory (DFT). The results of the study showed that lovastatin and simvastatin might be considered as lead compounds for further development for COVID-19 main protease inhibitors.

Insilico drug repurposing using FDA approved drugs against Membrane protein of SARS-CoV-2

“…The energy minimized drug database was used for docking-based virtual screening using PyRx database displayed acceptable binding energy score lower than -7.0 kcal/mol 38,54,55 .…”

Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study

“…The computational approach has been extensively explored in studies of possible drugs against infection by SARS-CoV-2. Sagaama et al [ 27 ] presented results of possible drugs complexed with SARS-CoV-2 proteins using theoretical level DFT and Molecular Docking as well as Jordaan et al [ 28 ] with results involving Simvastatin, Lovastatin, Oxacilin, podophyllotoxin, gefitinib with SARS-CoV-2 main protease. As a consequence, the main goal of this article is to present the result of the study of an interaction between ( R and S )-Linezolid with RBD of SARS-CoV-2 spike protein in complex with human ACE2.…”

Delineating binding potential, stability of Sulforaphane‐N‐acetyl‐cysteine in the active site of histone deacetylase 2 and testing its cytotoxicity against distinct cancer lines through stringent molecular dynamics, DFT and cell‐based assays

“…Analyzing these orbitals sheds light on the relative affinities of various inhibitors toward a specific biological target. The energy gap between HOMO and LUMO is usually used to estimate the feasibility of charge transfer and consequently the bioactivity (Jordaan et al., 2020). The calculated HOMO and LUMO orbitals of SNF‐NAC are −0.018416 and 0.061947 eV, respectively (Table 2).…”

“…The ligand molecule and the interacting residues in the protein were treated as the QM (Quantum Mechanics) region, while the rest of the protein was treated as the MM (Molecular Mechanics) region by applying Berke's three‐parameter exchange potential and Lee‐Yang‐Parr correlation functional (B3LYP) and 6–31G** basis set (Murphy et al., 2000). Properties such as Highest Occupied Molecular Orbitals (HOMO), Lowest Unoccupied Molecular Orbitals (LUMO) apart from electronic features of the molecules were estimated (Jordaan et al., 2020; Kollar & Frecer, 2017).…”