Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein
Authors
Yu-meng Chen
aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Jin-lai Wei
bDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
Rui-si Qin
aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Jin-ping Hou
cGeneral Surgery of Neonatal Surgery, Liangjiang District, Children's Hospital of Chongqing Medical University, Chongqing, PR China
Guang-chao Zang
aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Guang-yuan Zhang
aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Ting-ting Chen
aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Keywords:
COVID-19, Chinese medicine, network pharmacology, antivirus
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, network pharmacology, antivirus
Author Biographies
Guang-yuan Zhang, aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
dPathogen Biology and Immunology Laboratory, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
Ting-ting Chen, aLaboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
dPathogen Biology and Immunology Laboratory, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, PR China
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