2. Academic Validation
  3. Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model

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

  • Virol J. 2023 Jan 31;20(1):18. doi: 10.1186/s12985-023-01971-x.
Cuiling Zhang 1,  Bingjie Wei 2,  Zirui Liu 1,  Wei Yao 3,  Yiquan Li 4,  Jing Lu 1,  Chenchen Ge 1,  Xiaoyang Yu 1,  Dapeng Li 1,  Yilong Zhu 5,  Chao Shang 6,  Ningyi Jin 7 8 9,  Xiao Li 10 11 12
Affiliations

Affiliations

  • 1 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Yujinxiang road, 573, Jingyue Economic and Technological Development Zone, Changchun, 130122, Jilin, People's Republic of China.
  • 2 Veterinary Medicine College, Northwest A&F University, Shaanxi, 712100, People's Republic of China.
  • 3 Healthcare Department, Agency for Offices Administration, 23 Xinwai Street, Haidian District, Beijing, 100082, People's Republic of China.
  • 4 Changchun University of Chinese Medicine, Changchun, People's Republic of China.
  • 5 Changchun University of Chinese Medicine, Changchun, People's Republic of China. 362976499@qq.com.
  • 6 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Yujinxiang road, 573, Jingyue Economic and Technological Development Zone, Changchun, 130122, Jilin, People's Republic of China. shangchao1290@126.com.
  • 7 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Yujinxiang road, 573, Jingyue Economic and Technological Development Zone, Changchun, 130122, Jilin, People's Republic of China. skylee6226@163.com.
  • 8 Changchun University of Chinese Medicine, Changchun, People's Republic of China. skylee6226@163.com.
  • 9 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People's Republic of China. skylee6226@163.com.
  • 10 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Yujinxiang road, 573, Jingyue Economic and Technological Development Zone, Changchun, 130122, Jilin, People's Republic of China. lixiao06@mails.jlu.edu.cn.
  • 11 Changchun University of Chinese Medicine, Changchun, People's Republic of China. lixiao06@mails.jlu.edu.cn.
  • 12 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People's Republic of China. lixiao06@mails.jlu.edu.cn.
PMID: 36721152 DOI: 10.1186/s12985-023-01971-x
Abstract

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.

Keywords

Animal model; Bafilomycin A1; SARS-CoV-2; Variants.

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