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. 2021 Feb 15:324:115134.
doi: 10.1016/j.molliq.2020.115134. Epub 2020 Dec 27.

Excited-state electronic properties, structural studies, noncovalent interactions, and inhibition of the novel severe acute respiratory syndrome coronavirus 2 proteins in Ripretinib by first-principle simulations

Fahad A Alharthi  1 , Nabil Al-Zaqri  1 , Ali Alsalme  1 , Afnan Al-Taleb  1 , T Pooventhiran  2 , Renjith Thomas  2 , D Jagadeeswara Rao  3
Affiliations

Excited-state electronic properties, structural studies, noncovalent interactions, and inhibition of the novel severe acute respiratory syndrome coronavirus 2 proteins in Ripretinib by first-principle simulations

Fahad A Alharthi et al. J Mol Liq. .

Abstract

Ripretinib is a recently developed drug for the treatment of adults with advanced gastrointestinal stromal tumors. This paper reports an attempt to study this molecule by electronic modeling and molecular mechanics to determine its composition and other specific chemical features via the density-functional theory (DFT), thereby affording sufficient information on the electronic properties and descriptors that can enable the estimation of its molecular bioactivity. We explored most of the physico-chemical properties of the molecule, as well as its stabilization, via the studies of the natural bond orbitals and noncovalent interactions. The electronic excitation, which is a time-dependent process, was examined by the time-dependent DFT with a CAM-B3LYP functional. The molecular docking study indicated that Ripretinib strongly docks with three known novel severe acute respiratory syndrome coronavirus 2 (SARS-n-CoV-2) proteins with a reasonably good docking score.

Keywords: Density-functional theory; Molecular docking; Ripretinib; Severe acute respiratory novel coronavirus 2; Time-dependent density-functional theory.

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Conflict of interest statement

Authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Optimized structure of ripretinib obtained by DFT (B3LYP/6-311G + (2d,p)) exhibiting the unique structure of the compound with two different halogens in the central ring.
Fig. 2
Fig. 2
Simulated UV–Vis spectrum of ripretinib by TD-DFT/CAM-B3LYP/6–311 + G(2d,p) in methanol employing the IEFPCM model and exhibiting two distinct UV absorptions.
Fig. 3
Fig. 3
Pictorial representation of the various MOs involved in the electronic transitions. HOMO is in the central ring, while LUMO is delocalized over the naphthydrin group.
Fig. 4
Fig. 4
MESP map of ripretinib indicating the surface-charge distribution contour.
Fig. 5
Fig. 5
ALIE of the ripretinib molecule.
Fig. 6
Fig. 6
Graph of NCI against the reduced density gradient and interaction energy.
Fig. 7
Fig. 7
Skeletal structures of the interactions between ripretinib and the 6 M03, 6 W63, and 6 LU7 proteins.
See this image and copyright information in PMC

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