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; Nabil Al-Zaqri; Ali Alsalme; Afnan Al-Taleb; T Pooventhiran; Renjith Thomas; D Jagadeeswara Rao

doi:10.1016/j.molliq.2020.115134

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

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

Authors

Fahad A Alharthi¹, Nabil Al-Zaqri¹, Ali Alsalme¹, Afnan Al-Taleb¹, T Pooventhiran², Renjith Thomas², D Jagadeeswara Rao³

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, Kerala, India.
³ Department of Physics, Dr. Lankapalli Bullayya College, Visakhapatnam, Andhra Pradesh, India.

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.