Phytochemical and antiviral investigation of Cynanchum acutum L. extract and derived semi-synthetic analogs targeting SARS-CoV-2 main protease

Abstract

Abstract Background The genus Cynanchum , family Apocynaceae is a group of climbing vines that have long been in folk medicine used as antitussives, analgesics, anticonvulsants, expectorants, diuretics, antifebriles, and tonics. Results Cynanchum acutum crude extract was investigated to determine its chemical composition through LC-ESI-TOF-MS/MS technique, where 46 hits were observed. Among these compounds, quercetin-3- O - β -galactoside was previously reported within the plant as a major component. This compound was isolated and purified using different chromatographic techniques, and its concentration was estimated using high-performance thin-layer chromatography (HPTLC). Two semi-synthetic derivatives were synthesized from this compound, namely 7-benzyl- and 7-bromoethyl quercetin-3- O - β -galactosides. Both analogs, which are more hydrophobic, were developed as an attempt to improve the physiochemical properties and, in turn, the pharmacokinetics of the parent compound. Our study also includes the determination of antiviral activity against COVID-19 of Cynanchum acutum crude extract along with quercetin-3- O - β -galactoside in addition to the two semi-synthesized derivatives. The antiviral assay revealed that the synthetic benzyl derivative of quercetin-3- O - β -galactoside demonstrated promising activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The potential molecular aspects of the parent and semi-synthetic analogs were highlighted through molecular modeling simulation of docking the compounds at the viral main protease (Mpro) binding pocket. In silico findings demonstrated significant affinity and residue-wise binding interactions in relation to the co-crystallized small molecule Mpro inhibitor. Conclusion Collectively, our study adds to the current knowledge of SARS-CoV-2 pharmacotherapy by introducing drug-like small molecules with potential activity profiles. Graphical abstract