1. Academic Validation
  2. 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.
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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