Virol J


. 2023 Jan 31;20(1):18.
doi: 10.1186/s12985-023-01971-x.
Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model


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

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.