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

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 tha...

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Bibliographic Details
Published in:Virology journal 2023-01, Vol.20 (1), p.18-18, Article 18
Main Authors: Zhang, Cuiling, Wei, Bingjie, Liu, Zirui, Yao, Wei, Li, Yiquan, Lu, Jing, Ge, Chenchen, Yu, Xiaoyang, Li, Dapeng, Zhu, Yilong, Shang, Chao, Jin, Ningyi, Li, Xiao
Format: Article
Language:English
Subjects:
Acidification
Alveolar Epithelial Cells
Alveoli
Animal model
Animals
Bafilomycin A1
Cell death
Coronaviruses
COVID-19
Cytotoxicity
Disease
Disease Models, Animal
Dosage and administration
Endothelial cells
Heterografts
Humans
Hybridization
Immunohistochemistry
Infections
Infiltration
Inflammation
Laboratories
Leukocytes (granulocytic)
Lungs
Macrolide antibiotics
Macrophages
Mice
Pathogens
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Testing
Transcription
Variants
Viral infections
Viruses
Xenografts
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Summary: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.
ISSN:1743-422X
1743-422X
DOI:10.1186/s12985-023-01971-x