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.
摘要：
2019年冠状病毒病是由SARS-CoV-2引起的全球大流行。其变异株的出现对临床治疗提出了相当大的挑战。因此,能够抑制SARS-CoV-2感染的药物，不管病毒变异，迫切需要。我们的结果表明，内体酸化抑制剂，巴弗洛霉素A1（Baf-A1），在500nM浓度下对SARS-CoV-2及其β和δ变体的病毒RNA合成具有抑制作用。此外，人肺异种移植小鼠模型用于研究Baf-A1的抗SARS-CoV-2作用。通过原位杂交和RT-PCR测定，发现Baf-A1显着抑制人肺异种移植物中的SARS-CoV-2复制。组织病理学检查显示，Baf-A1减轻了SARS-CoV-2诱导的人肺异种移植物中粒细胞和巨噬细胞的弥漫性炎症浸润和肺泡内皮细胞死亡。此外,免疫组织化学分析表明，Baf-A1减少了SARS-CoV-2感染的人肺异种移植物的炎症渗出和浸润。因此,Baf-A1可能是SARS-CoV-2治疗的候选药物。
