New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods: In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results: The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions: These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.