Azole derivatives inhibit the binding of the RBD domain of SARS-Cov-2 against host ACE2 in in vitro assays

Abstract

The reuse of medicines is a practical and rapid response when early solutions are required for sudden-onset health problems such as SARS-CoV-2, the causative agent of the COVID-19 pandemic during the years 2020 - 2021. In this study we set out to determine by in silico assays with bioinformatics tools using the Swiss Dock online server and in vitro by enzyme-linked immunosorbent assays whether azole derivatives (such as fluconazole, secnidazole, clotrimazole) and ivermectin, can inhibit the interaction between human ACE2 and the RBD domain of SARS-CoV-2 S protein. The result of the docking of azoles and ivermectin showed a significant inhibitory action against RBD of SARS-CoV- 2 S protein and the binding energy. Since the results obtained in the in vitro assays showed a significant inhibition absorbance (OD value < 0.611) of the binding of hACE2 and the SARS-CoV-2 RBD, our results suggest that these azole derivatives can be considered as potential therapeutic candidates. This may suggest that the drugs studied can be used individually or in therapeutic combinations in trials to evaluate effectiveness in patients suffering from COVID-19 both early in the infection and in late stages. Secnidazole and fluconazole are commercially available and affordable drugs.