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抗组胺药和瑞德西韦联用可减少 SARS-CoV-2 复制并减轻炎症诱导的小鼠肺损伤。

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

机构信息

College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.

出版信息

Zool Res. 2022 May 18;43(3):457-468. doi: 10.24272/j.issn.2095-8137.2021.469.

DOI:10.24272/j.issn.2095-8137.2021.469
PMID:35503561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9113965/
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 , 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.

摘要

新型冠状病毒病（COVID-19）是由 SARS-CoV-2 感染引起的免疫介导的炎症性疾病，抗炎和抗病毒疗法的联合应用预计将提供临床获益。我们最近证明，肥大细胞（MCs）是 SARS-CoV-2 引发的过度炎症的重要介质。我们还表明，刺突蛋白诱导的 MC 脱颗粒引发肺泡上皮炎症，导致屏障破坏，并提示抗组胺药作为 MC 稳定剂的非适应证使用，以阻断脱颗粒，从而抑制炎症和预防肺损伤。在这项研究中，我们强调了 MCs 在 SARS-CoV-2 诱导的肺损伤中的重要作用，并证明了在 SARS-CoV-2 感染的小鼠中联合使用抗组胺药和抗病毒药物瑞德西韦的益处。具体而言，SARS-CoV-2 刺突蛋白诱导的 MC 脱颗粒导致肺泡毛细血管损伤，而用抗组胺药预处理肺微血管内皮细胞可防止黏附连接的破坏；可以预见的是，抗病毒药物瑞德西韦与抗组胺药氯雷他定（HR1 拮抗剂）联合使用，可抑制病毒复制和炎症，从而大大减轻肺损伤。我们的研究结果强调了 MCs 在 SARS-CoV-2 诱导的炎症和肺损伤中的关键作用，并为 COVID-19 治疗提供了一种可行的联合抗病毒和抗炎治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/a049f4f2dc50/zr-43-3-457-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/f5d9cd0b0fcb/zr-43-3-457-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/7feeb2f8e811/zr-43-3-457-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/550c5587d18a/zr-43-3-457-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/a049f4f2dc50/zr-43-3-457-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/f5d9cd0b0fcb/zr-43-3-457-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/b3762f0fbf0c/zr-43-3-457-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/7feeb2f8e811/zr-43-3-457-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/9113965/550c5587d18a/zr-43-3-457-4.jpg
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