ABSTRACT
Objective: To explore the potential active components of Chaiyin particles (CYPs) in the treatment of coronavirus disease 2019 (COVID-19) and their mechanism of action using network pharmacology and molecular docking technology. Methods: Based on the components of CYPs, we obtained potential targets of the interaction between CYPs and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The potential targets were analyzed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The key active components of CYPs were subjected to molecular docking with 3-chymotrypsin-like protease, angiotensin-converting enzyme II (ACE2), RNA-dependent RNA polymerase, and papain-like protease. The components that may bind to the key target proteins of SARS-CoV-2 were screened to obtain the potential active components, targets and pathways for CYP treatment of COVID-19. The above-described network analysis results were then verified experimentally. Results: CYPs may prevent and treat COVID-19 by inhibiting the release of inflammatory factors such as IL-6 and TNF-alpha;participating in the AGE-Rage signaling pathway, the HIF-1 signaling pathway, and other anti-inflammatory, antiviral, and immune regulatory signaling pathways;and blocking ACE2 via fortunellin and baicalin. Conclusion: This work illustrated that CYPs mainly play an anti-inflammatory and immunomodulatory role in COVID-19 prevention and treatment. The potential active components and molecular mechanism of CYPs can provide theoretical support and a pharmacological basis for further development and utilization of CYPs in the prevention and treatment of COVID-19. These results provide important insights into future studies of Traditional Chinese medicines (TCMs) modernization and prevention.
ABSTRACT
According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P<0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P<0.05, P<0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P<0.01). In vitro results showed that TC_(50), TC_0, IC_(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.