Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model

文献类型： 外文期刊

第一作者： Zhang, Cuiling

作者： Zhang, Cuiling;Liu, Zirui;Lu, Jing;Ge, Chenchen;Yu, Xiaoyang;Li, Dapeng;Shang, Chao;Jin, Ningyi;Li, Xiao;Wei, Bingjie;Yao, Wei;Li, Yiquan;Zhu, Yilong;Jin, Ningyi;Li, Xiao;Jin, Ningyi;Li, Xiao

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关键词： Bafilomycin A1; Animal model; SARS-CoV-2; Variants

期刊名称：VIROLOGY JOURNAL （ 影响因子：4.8； 五年影响因子：3.9 ）

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年卷期： 2023 年 20 卷 1 期

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收录情况： SCI

摘要： Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM. Moreover, the human lung xenograft mouse model was used to investigate the anti-SARS-CoV-2 effect of Baf-A1. It was found that Baf-A1 significantly inhibited SARS-CoV-2 replication in the human lung xenografts by in situ hybridization and RT-PCR assays. Histopathological examination showed that Baf-A1 alleviated SARS-CoV-2-induced diffuse inflammatory infiltration of granulocytes and macrophages and alveolar endothelial cell death in human lung xenografts. In addition, immunohistochemistry analysis indicated that Baf-A1 decreased inflammatory exudation and infiltration in SARS-CoV-2-infected human lung xenografts. Therefore, Baf-A1 may be a candidate drug for SARS-CoV-2 treatment.

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