Targeting SARS-CoV-2 main protease 3CL pro and human ACE2 with Paeonia Phytochemicals by in silico and in vitro Studies in Terms of Possible COVID- 19 Therapeutics

Abstract

Abstract As important medicinal herbs, Paeonia species have been used in ancient medicine. Although its therapeutic potential is well known, the potential efficacy of Paeonia phytochemicals against the emerging coronavirus (SARS-CoV-2) has yet to be tested. This study selected seventy-six Paeonia compounds to determine their potential druggable impact on SARS-CoV-2 main protease (3CLpro) and human ACE2 proteins. Structure-based virtual screening (SBVS) approach was performed by PyRx molecular docking software, including the Open Babel v2.4 and AutoDock 4.2.6 tools. The lowest affinity score and desired hydrogen bonding interactions were selected, and SwissADME was used to predict drug-likeness and pharmacokinetics properties. In addition, the potential cytotoxic effect of five Paeonia root extracts was tested in cancer (HCT116 and HeLa) and fibroblast (HFF) cell lines. The results showed that nine Paeonia ligands (catechin, apigenin, palbinone, kaempferol, paeoniflorigenone, eriodictyol, paeonilactone C, cassythicine, and 3-O-methylquercetin) were able to interact with SARS-CoV-2 at high affinity (from − 7.5 to -9.0 kJ/mol), as possible SARS-CoV-2 inhibitors. Molecular dynamics simulation (MDS) analysis revealed that five of these phytochemicals -cathecin, apigenin, palbinone, paeoniflorigenone, and eriadictyol- have the potential to act as effective compounds. In addition, the plant extracts at low concentrations is not cytotoxic for selected cell lines. Overall, this study points to the inhibitory potential of Paeonia phytochemicals as novel therapeutics against SARS-CoV-2. Their druggable potential can be tested in vivo in further studies.