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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.

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Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response and Ca2+ imbalance, and triggered the mitochondrial apoptotic pathway. The aim of this study was to explore the mechanisms by which Apoptin exhibited anti-tumor effects on the HepG-2 cells. The intracellular level of calcium (Ca2+) was induced by ER stress and determined by electron microscopy, flow cytometry and fluorescence staining. Mitochondrial injury was determined by mitochondrial membrane potential, electron microscopy. Western blotting was used to investigate the levels of key proteins in the ER stress and the apoptotic pathway in the mitochondria. The relationship between Ca2+ level and apoptosis on Apoptin-treating cells was analyzed using Ca2+ chelator (BAPTA-AM), flow cytometry and fluorescence staining. We also investigated the in vivo effects of Ca2+ imbalance on the mitochondrial apoptotic pathway using the tumor tissues xenografted on nude mice. In vitro and in vivo experiments showed that Apoptin caused an imbalance in Ca2+, and increased the expression levels of Smac/Diablo and Cyto-C. In summary, Apoptin induced apoptosis in HepG-2 cells via Ca2+ imbalance-triggered mitochondrial apoptotic pathway. This study provided a new direction for antitumor research in Apoptin.