%0 Journal Article
%T Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model.
%A Zhang C
%A Wei B
%A Liu Z
%A Yao W
%A Li Y
%A Lu J
%A Ge C
%A Yu X
%A Li D
%A Zhu Y
%A Shang C
%A Jin N
%A Li X
%J Virol J
%V 20
%N 1
%D 01 2023 31
%M 36721152
%F 5.913
%R 10.1186/s12985-023-01971-x
%X 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.