HOMO and LUMO energies are valuable in analyzing the chemical potential (µ), hardness (η), and electrophilicity (ω) that reveal the electronic donor-acceptor reactivity of the individual ligands and are crucial in assessing their reactivities toward proteins of the virus and the human receptor . The results are summarized in Table . The more the ligand will be reactive, the more it will participate in electronic interactions and bond formation with protein. The electrophilicity index (𝜔 = 𝜇 2 /(2 * 𝜂) measures a molecule's ability to act as an electron sink-the higher its value, the stronger the ligand's electron sink property. The electrophilicity index provides a magnitude of the energy stabilization of a molecule when it gains an extra amount of electron density during the interaction. The electrophilicity index comprises the tendency of an electrophile to earn an excessive amount of electron density, given by the chemical potential µ and the resistance of a molecule to exchange electron density during an interaction, provided by the hardness h. Therefore, a suitable electrophile is characterized by an excessive µ value and a little h value. The electrophilicity index rendered a powerful apparatus for studying the reactivity of drug molecules . 𝜔 values of all studied molecules except EIDD-2801 are higher than ACE2 and b6 sheets. Thus, electron donor-acceptor affinity of the proteins -drugs increases with increasing the value of 𝜔. However, the electrophilicity fails to explain the orbital localization in the case of proteins interacting, as shown in Table and Figures 1. In this case, the hardness and chemical