Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein
Yu-Meng Chen, Jin-Lai Wei, Rui-Si Qin, Jin-Ping Hou, Guang-Chao Zang, Guang-Yuan Zhang, Ting-Ting Chen
Pharmaceutical Biology, doi:10.1080/13880209.2022.2063341
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.
Disclosure statement The authors declare no conflicts of interest. Author contributions J.P.H. and R.S.Q. performed the bioinformatic analysis. Y.M.C. and J.L.W. wrote the paper; and T.T.C. contributed to the final version of the manuscript, as well as read and approved it; the rest of the authors contributed to the modification of the manuscript. All authors read and approved the manuscript.
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