Structural investigations, quantum mechanical studies on proton and metal affinity and biological activity predictions of selpercatinib

Nabil Al-Zaqri; T Pooventhiran; Fahad A Alharthi; Utsab Bhattacharyya; Renjith Thomas

doi:10.1016/j.molliq.2020.114765

Structural investigations, quantum mechanical studies on proton and metal affinity and biological activity predictions of selpercatinib

J Mol Liq. 2021 Mar 1:325:114765. doi: 10.1016/j.molliq.2020.114765. Epub 2020 Nov 13.

Authors

Nabil Al-Zaqri^{1

2}, T Pooventhiran³, Fahad A Alharthi¹, Utsab Bhattacharyya³, Renjith Thomas³

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Chemistry, College of Science, Ibb University, P. O. Box 70270, Ibb, Yemen.
³ Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, Kerala, India.

Abstract

Cancer of the lungs and thyroid is particularly difficult to manage and treat. Notably, selpercatinib has recently been suggested as an effective drug to combat these diseases. The entire world is currently tackling the pandemic caused by the SARS-CoV-19 virus. Numerous pharmaceuticals have been evaluated for the management of the disease caused by SARS-CoV-19 (i.e., COVID-19). In this study, selpercatinib was proposed as a potential inhibitor of different SARS-CoV-19 proteins. Several intriguing effects of the molecule were found during the conducted computational investigations. Selpercatinib could effectively act as a proton sponge and exhibited high proton affinity in solution. Moreover, it was able to form complexes with metal ions in aqueous solutions. Specifically, the compound displayed high affinity towards zinc ions, which are important for the prevention of virus multiplication inside human cells. However, due to their charge, zinc ions are not able to pass the lipid bilayer and enter the cell. Thus, it was determined that selpercatinib could act as an ionophore, effectively transporting active zinc ions into cells. Furthermore, various quantum mechanical analyses, including energy studies, evaluation of the reactivity parameters, examination of the electron localisation and delocalisation properties, as well as assessment of the nonlinear optical (NLO) properties and information entropy, were conducted herein. The performed docking studies (docking scores -9.3169, -9.1002, -8.1853 and -8.1222 kcal mol^-1) demonstrated that selpercatinib strongly bound with four isolated SARS-CoV-2 proteins.

Keywords: DFT; Docking; ELF; Proton affinity; Selpercatinib.