■氧固醇结合蛋白(OSBP)因其在脂质运输中的关键作用而闻名,促进高尔基体和内质网膜之间的胆固醇交换。尽管它在细胞过程中已经确立了功能,其是否参与冠状病毒复制仍不清楚.
■在这项研究中,我们研究了OSBP在冠状病毒复制中的作用,并探索了一种新型OSBP结合化合物的潜力,ZJ-1,作为抗冠状病毒的抗病毒剂,包括SARS-CoV-2.我们利用生化和细胞测定的组合来阐明OSBP与SARS-CoV-2非结构蛋白(Nsps)和其他病毒蛋白之间的相互作用。
■我们的研究结果表明,OSBP正调节冠状病毒的复制。此外,ZJ-1治疗导致OSBP水平降低,并表现出对多种冠状病毒的有效抗病毒作用.通过我们的调查,我们确定了OSBP和SARS-CoV-2Nsps之间的特定相互作用,特别是Nsp3,Nsp4和Nsp6,它们参与双膜囊泡的形成,这是病毒复制的关键步骤。此外,我们观察到Nsp3a.a.1-1363,Nsp4和Nsp6靶向囊泡相关膜蛋白(VAMP)相关蛋白B(VAP-B),将OSBP固定在ER膜上。有趣的是,OSBP和VAP-B之间的相互作用被Nsp3a.a.1-1363破坏,部分被Nsp6损害。此外,我们确定了SARS-CoV-2或f7a,orf7b,和orf3a作为额外的OSBP目标,OSBP有助于他们的稳定。
■我们的研究强调了OSBP在冠状病毒复制中的重要性,并将其确定为开发针对SARS-CoV-2和其他冠状病毒的抗病毒疗法的有希望的靶标。这些发现强调了针对OSBP的干预措施在对抗冠状病毒感染方面的潜力。
UNASSIGNED: Oxysterol-binding protein (OSBP) is known for its crucial role in lipid transport, facilitating cholesterol exchange between the Golgi apparatus and endoplasmic reticulum membranes. Despite its established function in cellular processes, its involvement in coronavirus replication remains unclear.
UNASSIGNED: In this study, we investigated the role of OSBP in coronavirus replication and explored the potential of a novel OSBP-binding compound, ZJ-1, as an antiviral agent against coronaviruses, including SARS-CoV-2. We utilized a combination of biochemical and cellular assays to elucidate the interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) and other viral proteins.
UNASSIGNED: Our findings demonstrate that OSBP positively regulates coronavirus replication. Moreover, treatment with ZJ-1 resulted in reduced OSBP levels and exhibited potent antiviral effects against multiple coronaviruses. Through our investigation, we identified specific interactions between OSBP and SARS-CoV-2 Nsps, particularly Nsp3, Nsp4, and Nsp6, which are involved in double-membrane vesicle formation-a crucial step in viral replication. Additionally, we observed that Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), which anchors OSBP to the ER membrane. Interestingly, the interaction between OSBP and VAP-B is disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, we identified SARS-CoV-2 orf7a, orf7b, and orf3a as additional OSBP targets, with OSBP contributing to their stabilization.
UNASSIGNED: Our study highlights the significance of OSBP in coronavirus replication and identifies it as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses. These findings underscore the potential of OSBP-targeted interventions in combating coronavirus infections.