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将止吐药甲氧氯普胺重新用于抗神经细胞中的登革热病毒感染。

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

机构信息

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

Front Cell Infect Microbiol. 2021 Feb 2;10:606743. doi: 10.3389/fcimb.2020.606743. eCollection 2020.

DOI:10.3389/fcimb.2020.606743
PMID:33634036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7902071/
Abstract

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 . An 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.

摘要

登革热病毒（DENV）通过埃及伊蚊传播给人类，是全球范围内的威胁。目前尚无有效的新药物用于抗登革热治疗，而药物再利用是治疗这种疾病的一种替代方法。多巴胺 2 受体（D2R）是与 DENV 感染呈正相关的宿主受体。甲氧氯普胺（MCP）是一种临床上用于控制登革热感染患者呕吐和恶心的 D2R 拮抗剂，被推测通过靶向 D2R 抑制 DENV 感染。在表达 D2R 的小鼠神经细胞系 Neuro-2a 中，噬斑测定显示 MCP 治疗具有抗病毒功效。然而，在不表达 D2R 的 BHK-21 细胞系中，MCP 治疗并未进一步抑制 DENV 感染。MCP 治疗或外源性给予中和 D2R 抗体均可阻断 DENV 结合。MCP 治疗还降低了 DENV dsRNA 复制和 DENV 诱导的神经元细胞毒性。一项研究证明了 MCP 对 DENV 诱导的中枢神经系统神经病变和死亡率的抗病毒作用。这些结果表明，针对 D2R 的止吐药 MCP 的再利用是一种针对 DENV 感染的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/3a9b1c326037/fcimb-10-606743-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/d79e7dde81fe/fcimb-10-606743-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/a6f3a969b415/fcimb-10-606743-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/87e887b378d1/fcimb-10-606743-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/70c571378113/fcimb-10-606743-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/3a9b1c326037/fcimb-10-606743-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/d79e7dde81fe/fcimb-10-606743-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/a6f3a969b415/fcimb-10-606743-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/87e887b378d1/fcimb-10-606743-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/70c571378113/fcimb-10-606743-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2f/7902071/3a9b1c326037/fcimb-10-606743-g005.jpg

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