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

作　　者：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 

机构地区：[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

出　　处：《Zoological Research》2022年第3期457-468,共12页动物学研究（英文）

基　　金：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);Key Project from the Chinese Academy of Sciences(QYZDB-SSWSMC059)。

摘　　要：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,SARSCoV-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.

关 键 词：SARS-CoV-2 Mast cell Remdesivir ANTIHISTAMINE Combinational therapy 

分 类 号：R965[医药卫生—药理学]