Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice

Meng-Li Wu; Feng-Liang Liu; Jing Sun; Xin Li; Jian-Ru Qin; Qi-Hong Yan; Xia Jin; Xin-Wen Chen; Yong-Tang Zheng; Jin-Cun Zhao; Jian-Hua Wang

doi:10.24272/j.issn.2095-8137.2021.469

Volume 43 Issue 3

May 2022

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Article Navigation > Zoological Research > 2022 > 43(3): 457-468

Meng-Li Wu, Feng-Liang Liu, Jing Sun, Xin Li, Jian-Ru Qin, Qi-Hong Yan, Xia Jin, Xin-Wen Chen, Yong-Tang Zheng, Jin-Cun Zhao, Jian-Hua Wang. Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice. Zoological Research, 2022, 43(3): 457-468. doi: 10.24272/j.issn.2095-8137.2021.469

Citation:

Meng-Li Wu, Feng-Liang Liu, Jing Sun, Xin Li, Jian-Ru Qin, Qi-Hong Yan, Xia Jin, Xin-Wen Chen, Yong-Tang Zheng, Jin-Cun Zhao, Jian-Hua Wang. Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice. Zoological Research, 2022, 43(3): 457-468. doi: 10.24272/j.issn.2095-8137.2021.469

Citation:

Meng-Li Wu, Feng-Liang Liu, Jing Sun, Xin Li, Jian-Ru Qin, Qi-Hong Yan, Xia Jin, Xin-Wen Chen, Yong-Tang Zheng, Jin-Cun Zhao, Jian-Hua Wang. Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice. Zoological Research, 2022, 43(3): 457-468. doi: 10.24272/j.issn.2095-8137.2021.469

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Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice

doi: 10.24272/j.issn.2095-8137.2021.469

Meng-Li Wu^{1, 2, #},
Feng-Liang Liu^{3, #},
Jing Sun^{4, #},
Xin Li²,
Jian-Ru Qin¹,
Qi-Hong Yan⁴,
Xia Jin¹,
Xin-Wen Chen²,
Yong-Tang Zheng^{3
,
,},
Jin-Cun Zhao^{4
,
,},
Jian-Hua Wang^{2, 4, 5
,
,}

1.
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China
2.
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
3.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
4.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
5.
University of Chinese Academy of Sciences, Beijing 100049, China

#Authors contributed equally to this work

Funds: This work was supported by the National Natural Science Foundation of China (82172242, 81873965), State Key Laboratory of Respiratory Disease, Guangzhou, China (SKLRD-OP-202207), National Key R&D Program of China (2020YFC0842000), Natural Science Foundation of Guangdong (2022A1515012053), and Key Project from the Chinese Academy of Sciences (QYZDB-SSW-SMC059)

More Information

Corresponding author: E-mail: zhengyt@mail.kiz.ac.cn; zhaojincun@gird.cn; wang_jianhua@gibh.ac.cn
Received Date: 2022-03-18
Accepted Date: 2022-04-19

Published Online: 2022-04-25

Publish Date: 2022-05-18

Abstract

Abstract

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.
- SARS-CoV-2,
- Mast cell,
- Remdesivir,
- Antihistamine,
- Combinational therapy

#Authors contributed equally to this work

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References(54)

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