The Extracts of Polygonum cuspidatum Root and Rhizome Block the Entry of SARS-CoV-2 Wild-Type and Omicron Pseudotyped Viruses via Inhibition of the S-Protein and 3CL Protease.

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.

Comparative bioactivity evaluation and chemical profiling of different parts of the medicinal plant Glycyrrhiza uralensis.

Glycyrrhiza uralensis is a popular medicinal plant worldwide. Its roots and rhizomes are used as the traditional Chinese medicine Gan-Cao. However, little is known on medicinal potential and chemistry of the other parts of the plant. In this work, the biological activities and chemical components of the roots, stems, leaves, and seeds of G. uralensis were investigated comparatively. The four parts exhibited different but noticeable biological activities. The chemicals in the four parts were globally characterized by liquid chromatography coupled with mass spectrometry (LC/MS) on a Thermo Vanquish UHPLC system connected to a Q-Exactive quadrupole Orbitrap mass spectrometer. By integrating molecular networking, compound spectral matching, MS2LDA-based substructure recognition, and reference standards comparison, a total of 1301 compounds were rapidly characterized. Three flavonoid C-glycosides were purified and their structures were identified by NMR spectroscopic analysis. Orthogonal partial least squares-discriminate analysis (OPLS-DA) further revealed 196 differential chemicals for the four parts. This work will promote the medicinal resource utilization of G. uralensis.

Integrated network pharmacology and molecular docking strategy to explore the mechanism of medicinal and edible Astragali Radix-Atractylodis Macrocephalae Rhizoma acting on pneumonia via immunomodulation.

Pneumonia refers to a death-causing infection. Astragali Radix (AR) and Atractylodis Macrocephalae Rhizoma (AMR) are widely used as traditional tonic and promising edible immunomodulatory herbal medicine, but the systemic mechanism is not well understood. Therefore, a strategy based on network pharmacology and molecular docking was designed to explore the systemic mechanism of AR-AMR acting on pneumonia. After a series of bioinformatics assays, seven kernel targets were obtained, including TNF, IL6, IFNG, IL1B, IL10, IL4, and TLR9. And seven key compounds were identified as the synergy components of AR-AMR acting on pneumonia, the four key compounds belonging to AR were (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)-7-chromanol, formononetin, quercetin, and kaempferol, the three key compounds belonging to AMR were atractylone, 14-acetyl-12-senecioyl-2E, 8E, 10E-atractylentriol, and α-Amyrin. The crucial pathways were mainly related to three modules, including immune diseases, infectious disease, and organismal systems. Collectively, these observations strongly suggest that the molecular mechanisms of AR-AMR regulating pneumonia were closely related to the correlation between inflammation and immune response. PRACTICAL APPLICATIONS: Astragali radix and Atractylodis macrocephalae rhizoma can be used as "medicine-food homology" for dietary supplement. AR and AMR are widely used as a traditional tonic and promising edible immunomodulatory herbal medicine. The AR-AMR herb pairs are used for compatibility many times in the recommended prescriptions in COVID-19 develop pneumonia in China. However, the ingredients and mechanisms of AR-AMR acting on Pneumonia via immunomodulation are unclear. In this paper, bioinformatics and network biology were used to systematically explore the mechanisms of the AR-AMR herb pairs in treatment of pneumonia, and further analyze the correlation mechanism between it and COVID-19 develop pneumonia. To sum up, our study reveals the interrelationships between components, targets, and corresponding biological processes of AR-AMR acting on pneumonia. Understanding these relationships may provide guidance and theoretical basis for the further application of AR-AMR herb pairs.