Interactive Deciphering Electron-mediating Characteristics of Rheum species and Potential Bioenergy-Steered Anti-COVID-19 RdRp Inhibitor

Background: Plant-based foods have been established as “natural medicines” for their potential pharmacological properties. Chinese rhubarb plants – belonging to Polygonaceae family, are traditionally used to ameliorate digestive system problems. This study evaluated the chemical profile and bioactivities of three Rheum species – R. officinale (RO), R. palmatum (RP), and R. tanguticum (RT) roots. Methods: Five crude root extracts – water (W), ethanol (EtOH), acetone (A), ethyl acetate (EA), and hexane (H) – were tested for phytochemical screening, antioxidant tests, HPLC analysis, and dual-chambered-MFCs for bioenergy production. Molecular docking analysis of chemical markers was implemented to establish its application for antiviral drug development. Significant findings: Both RO and RP possessed the highest polyphenols and flavonoids in EA and H extracts, respectively. RT-A contained the highest phytochemical constituents compared to other solvent extracts. The RT-A extract demonstrated the highest scavenging activity against DPPH (IC₅₀=0.042±0.000mg/mL) and contained the highest FRAP value (1051.238±7.154mg Trolox/g). Bioenergy evaluation showed that RO-W exhibited the highest bioenergy-stimulating capabilities (1.84 fold power amplification). Furthermore, rhein from the same extract possessed the efficient electron-shuttling ability. Molecular docking analysis showed that Rheum metabolites inhibited key enzymes (i.e. RdRp and ACE-2) of SARS-CoV-2 viral replication process. Rhein (∆G=-6.9 kcal/mol) and chrysophanol (∆G=-4.8 kcal/mol) owned the highest binding affinity with RdRp and ACE-2 of SARS-CoV-2, respectively. This study provided a novel basis for the potential utilization of Rheum species as a renewable material for bioprocess engineering and electro-fermentation. Moreover, molecular docking analyses on Rheum species metabolites against SARS-CoV-2 offered a new rationale as a medicinal herb for antiviral drug development.