Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells

Frontiers in Cellular and Infection Microbiology

Vu Thi Hanh¹  Thai Quoc Nguyen²  Min-Ru Ho³  Ting-Jing Shen³  Ming-Kai Jhan³  Chiou-Feng Lin⁴ 

[1]Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[2]International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[3]Centre for Hematology and Blood Transfusion, Bach Mai Hospital, Hanoi, Vietnam

[4]Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[5]International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[6]Centre for Tropical Diseases, Bach Mai Hospital, Hanoi, Vietnam

[7]Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

[8]Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[9]Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

[10]Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

[11]Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan, Taiwan

关键词: dengue virus;    antiemetics;    metoclopramide;    antiviral;    dopamine receptor;   

DOI  :  10.3389/fcimb.2020.606743

来源: Frontiers

【 摘 要 】

Dengue virus (DENV) is transmitted by Aedes mosquitoes to humans and is a threat worldwide. No effective new drugs have been used for anti-dengue treatment, and repurposing drugs is an alternative approach to treat this condition. Dopamine 2 receptor (D2R) is a host receptor positively associated with DENV infection. Metoclopramide (MCP), a D2R antagonist clinically used to control vomiting and nausea in patients with DENV infection, was putatively examined for inhibition of DENV infection by targeting D2R. In the mouse neural cell line Neuro-2a with D2R expression, a plaque assay demonstrated the antiviral efficacy of MCP treatment. However, in the cell line BHK-21, which did not express D2R, MCP treatment caused no further inhibition of DENV infection. Either MCP treatment or exogenous administration of a neutralizing D2R antibody blocked DENV binding. Treatment with MCP also reduced DENV dsRNA replication and DENV-induced neuronal cell cytotoxicity in vitro. An in vivo study demonstrated the antiviral effect of MCP against DENV-induced CNS neuropathy and mortality. These results showed that repurposing the D2R-targeting antiemetic MCP is a potential therapeutic strategy against DENV infection.

【 授权许可】

CC BY