Abstract
Context: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 N).
Objective: To identify novel molecular therapeutic targets for SARS-CoV-2.
Materials and methods: Traditional Chinese medicine targets and virus-related genes were identified with network pharmacology and big data analysis. Folic acid was singled out by molecular docking, and its potential target SARS-CoV-2 N was identified. Inhibition of SARS-CoV-2 N of folic acid was verified at the cellular level.
Results: In total, 8355 drug targets were potentially involved in the inhibition of SARS-CoV-2. 113 hub genes were screened by further association analysis between targets and virus-related genes. The hub genes related compounds were analysed and folic acid was screened as a potential new drug. Moreover, molecular docking showed folic acid could target on SARS-CoV-2 N which inhibits host RNA interference (RNAi). Therefore, this study was based on RNAi to verify whether folic acid antagonises SARS-CoV-2 N. Cell-based experiments shown that RNAi decreased mCherry expression by 81.7% ( p < 0.001). This effect was decreased by 8.0% in the presence of SARS-CoV-2 N, indicating that SARS-CoV-2 N inhibits RNAi. With increasing of folic acid concentration, mCherry expression decreased, indicating that folic acid antagonises the regulatory effect of SARS-CoV-2 N on host RNAi.
Discussion and conclusions: Folic acid may be an antagonist of SARS-CoV-2 N, but its effect on viruses unclear. In future, the mechanisms of action of folic acid against SARS-CoV-2 N should be studied.
Keywords: COVID-19; Chinese medicine; antivirus; network pharmacology.
【저자키워드】 COVID-19, Chinese medicine, Network pharmacology., antivirus, 【초록키워드】 coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, hub genes, molecular docking, network pharmacology, Traditional Chinese medicine, antiviral effects, docking, inhibition, Folic acid, global pandemic, Regulatory, Nucleocapsid phosphoprotein, Data analysis, RNA interference, drug target, target, targets, experiment, molecular, mechanism, association, cellular, RNAi, Concentration, Analysis, therapeutic target, Compound, Chinese, material, SARS-CoV-2 N, mCherry, antagonist, Host, Genes, mCherry expression, shown, identify, virus, involved, inhibit, analysed, screened, Phosphoprotein, Traditional, 【제목키워드】 Protein, inhibitor, SARS-CoV-2 nucleocapsid,