In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2

Abstract

Isatin (1H-indole-2,3-dione)-containing compounds have been shown to possess several remarkable biological activities. We had previously explored a few isatin-based imidazole derivatives for their predicted dual activity against both inflammation and cancer. We explored 47 different isatin-based derivatives (IBDs) for other potential biological activities using in silico tools and found them to possess anti-viral activity. Using AUTODOCK tools, the binding site, binding energy, inhibitory constant/Ki and receptor-ligand interactions for each of the compounds was analyzed against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The partition coefficient (logP) values were predicted using MedChem Designer tool. Based on the best Ki, binding energy and the ideal range of logP (between 1.0-3.0), 10 out of total 47 compounds were deemed to be prospective RdRp inhibitors. Some of these compounds gave better Ki, binding energy and logP values when compared to standard RdRp inhibitors such as remdesivir (Ki = 15.61 μM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor which is widely used for critical care of COVID-19 patients. The same in silico parameters were assessed for 9 other popular RdRp inhibitors (other than remdesivir), which were earlier used to target RdRp of other viruses, and are now repurposed to target SARS-CoV-2 RdRp. The results showed that the 10 selected isatin-based derivatives (IBDs) could be further explored for activity against SARS-Cov-2. In the present study we evaluated the efficacy of these compounds in silico.