Volume 43 Issue 3
May  2022
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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

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
#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
  • 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.
  • #Authors contributed equally to this work
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