Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model

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.

Identification of diphenylurea derivatives as novel endocytosis inhibitors that demonstrate broad-spectrum activity against SARS-CoV-2 and influenza A virus both in vitro and in vivo

“…We, therefore, infected TMPRSS2-expressing Vero-E6 cells treated with the DPUDs with SARS-CoV-2 (D614G) in presence/absence of camostat. We also included BafA1 and niclosamide as they have been reported to attenuate SARS-CoV-2 infection [ 19 , 69 , 71 , 72 ]. BafA1 is a vATPase inhibitor and niclosamide is a protonophore that disrupts proton gradient, and both the drugs potently inhibit endosomal acidification.…”

Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection

“…However, it was reported that MHV infection induces ER-derived double-membrane vesicles (DMVs) independent of the autophagic pathway through the hijacking of the host cell ERassociated degradation (ERAD) machinery [46]. Recently, reports showed that applying the inhibitors that block the fusion between autophagosomes and lysosomes to coronaviruses' infected cells can potentially decrease the viral infection [47][48][49]. We, therefore, assessed whether G42 inhibits infection of MHV in its host cells.…”