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Computational Study of the Correlation of in-vitro Antiviral Activities Against SARS-CoV-2 with Different Theoretical Descriptors

Abstract:

The electrostatic potential (V(r)), the average local ionization energy (I(r)), the relative hardness (ηrel), the electron affinity (EA), the ionization potential (IP), the electronegativity (χ), the hardness (η) and the electrophilicity (ω) were tested as theoretical descriptors of the reported in-vitro antiviral activities against SARS-CoV-2 for seven different compounds with the same set of controlled variables: chloroquine, favipiravir, nafamostat, nitazoxanide, penciclovir, remdesivir, rivabirin, in order to obtain information about the electronic nature of the hosting sites in the virus. Results indicate that the hardness of the studied drugs correlates moderately well with the biological activity, which gives some insights to infer in terms of the HSAB principle of Pearson, that the electrostatic interactions must predominate in the virus hosting sites and that these areas have low polarizability. When a multiple correlation analysis is performed, the correlation improves when the conceptual hardness (η), Vmin, and the molecular volume are considered, which suggests that the interaction of the molecules with the preferred hard hosting sites should be negatively affected by the volume of the selected drug and that Vmin contributes to the correlation.