Open AccessCombinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice
Author(s) -
MengHao Wu,
FengLiang Liu,
Jing Sun,
Xin Li,
Jianglei Qin,
Qihong Yan,
Xia Jin,
Xinwen Chen,
YongTang Zheng,
Jincun Zhao,
Jianhua Wang
Publication year - 2022
Publication title -
zoological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 19
ISSN - 2095-8137
DOI - 10.24272/j.issn.2095-8137.2021.469
Subject(s) - inflammation , medicine , degranulation , pharmacology , immunology , lung , receptor
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.