AUTHOR=Ma-Lauer Yue , Li Pengyuan , Niemeyer Daniela , Richter Anja , Pusl Konstantin , von Brunn Brigitte , Ru Yi , Xiang Chengyu , Schwinghammer Sebastian , Liu Jia , Baral Priya , Berthold Emilia J. , Qiu Haibo , Roy Avishek , Kremmer Elisabeth , Flaswinkel Heinrich , Drosten Christian , Jin Zhendong , von Brunn Albrecht 

TITLE=Oxysterole-binding protein targeted by SARS-CoV-2 viral proteins regulates coronavirus replication

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1383917

DOI=10.3389/fcimb.2024.1383917

ISSN=2235-2988

ABSTRACT=Oxysterol-binding protein (OSBP) functions as a critical lipid transporter, facilitating the exchange of cholesterol between the Golgi apparatus and endoplasmic reticulum membranes.We show that OSBP plays a critical role in the positive regulation of coronavirus replication. In addition, we introduce a novel OSBP-binding compound, ZJ-1, which reduces OSBP levels and exhibits potent antiviral effects against several coronaviruses, including SARS-CoV-2. Through our investigation, we identified the SARS-CoV-2 non-structural proteins Nsp3, Nsp4, and Nsp6as key interactors with OSBP, particularly involved in double-membrane vesicle formation. In addition, Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), a critical factor in anchoring OSBP to the ER membrane.Notably, the interaction between OSBP and VAP-B is substantially disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, SARS-CoV-2 orf7a, orf7b, and orf3a were identified as additional OSBP targets, with OSBP contributing to their stabilization. Our findings highlight OSBP as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses.