Computational investigation on the potential inhibitory effect of fungal metabolites against viral RdRp of SARS-CoV-2 and HCV

Abstract

The novel emergence of Coronavirus Disease 2019 (COVID-19) quickly expanded around the globe, becoming one of the biggest current viral pandemics, posing a serious threat to human beings. The current research involved an evaluation of 188 fungal secondary metabolites for their efficacy as antiviral agents against the newly emerged RNA-dependent RNA polymerase (RdRp) of coronavirus through computer-based techniques. HCV polymerase was chosen as a standard. A cascade of blind and targeted molecular docking was performed to identify the most effective compounds to inhibit viral enzymes. Following this, the three chosen compounds were assessed by MD (molecular dynamics) simulations. Besides, the pharmacokinetics of the fungal secondary metabolites was investigated by SwissADME webserver. Armed with molecular docking results, Sterostrein B, Sterostrein C and Ganodermacetal delineated higher binding energies among all studied compounds. According to MD and SwissADME results, it can be postulated that two fungal metabolites, Sterostrein B, Sterostrein C demonstrated superior results with regard to potent complex formation, protein instability, and pharmacokinetic features in comparison to other fungal compounds. These two fungal secondary metabolites exhibit promoted inhibitory activities against two viral targets, in particular SARS-CoV-2 RdRp. In total, Sterostrein B, Sterostrein C can be suggested for further investigation as potential drug candidates to inhibit COVID-19.