Transcriptome-based exploration of the effect of Arbidol on HCoV-OC43 infection-induced activation of the neurotrophin signaling pathway
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1. Guangdong Medical University, Zhanjiang 524023, China. 2. Department of Critical Care Medicine, Dongguan Institute of Respiratory and Critical Care Medicine, the 10th Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan 523059. 3. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500. 4. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000. 5. Guangzhou Laboratory, Guangzhou 510000. 6. Guangzhou key laboratory for clinical rapid diagnosis and early warning of infectious diseases, Guangzhou 510000. 7. State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 519020

Clc Number:

R-33

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    Abstract:

    Objective To analyze the influence of arbidol(ARB) on HCoV-OC43-induced activation of host signaling pathways and to explore the correlation between the anti-inflammatory activity of ARB and its effect on the neurotrophin signaling pathway. Methods HRT-18 cells were infected with OC43 and treated with ARB. After 96 hours, total RNA was extracted, transcriptomic analysis was performed to identify differentially expressed genes(DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed to identify potential biological processes and signaling pathways related to ARB treatment. RT-qPCR was used to verify the inhibitory effect of ARB on the expression of important molecules in the neurotrophin pathway. Results ARB treatment at high, medium, and low doses(6, 2 and 0. 67 μg/ mL)resulted in 9459, 4186, and 1744 DEGs, respectively, compared with the virus-infected control group. GO analysis showed that ARB mainly affected biological processes of cotranslational protein targeting to membrane, cellular components such as focal adhesion and cell-substrate junction, and molecular functions such as cadherin binding. KEGG analysis showed that apoptosis and neurotrophin signaling pathways related to coronavirus infection were significantly enriched, and ARB had a significant inhibitory effect on MAPK, PI3K, and NF-κB in the neurotrophin signaling pathway. RT-qPCR analysis revealed that ARB significantly inhibited mRNA expression of PIK3CA, AKT, TRAF-6, Bax, p38, and c-Jun. Conclusions This study suggests that ARB can be used for treatment of neuroinflammation caused by coronavirus infection.

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History
  • Received:August 26,2022
  • Online: August 18,2023
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