Ma-Lauer, Y.* ; Li, P.* ; Niemeyer, D.* ; Richter, A.* ; Pusl, K.* ; von Brunn, B.* ; Ru, Y.* ; Xiang, C.* ; Schwinghammer, S.* ; Liu, J.* ; Baral, P.* ; Berthold, E. ; Qiu, H.* ; Roy, A.* ; Kremmer, E.* ; Flaswinkel, H.* ; Drosten, C.* ; Jin, Z.* ; von Brunn, A. *
     
    
        
Oxysterole-binding protein targeted by SARS-CoV-2 viral proteins regulates coronavirus replication.
    
    
        
    
    
        
        Front. Cell. Infect. Microbiol. 14:1383917 (2024)
    
    
    
      
      
	
	    INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Nsp3 ; Nsp4 ; Nsp6 ; Osbp ; Sars-cov-2 ; Vap-b ; Coronavirus; Hepatitis-c Virus; Enterovirus Replication; Natural Compound; Sars; Osw-1
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2024
    
 
    
        Prepublished in Year
        0
    
 
    
        HGF-reported in Year
        2024
    
 
    
    
        ISSN (print) / ISBN
        2235-2988
    
 
    
        e-ISSN
        2235-2988
    
 
    
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	    Volume: 14,  
	    Issue: ,  
	    Pages: ,  
	    Article Number: 1383917 
	    Supplement: ,  
	
    
 
    
        
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            Frontiers
        
 
        
            Publishing Place
            Lausanne
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30202 - Environmental Health
    
 
    
        Research field(s)
        Lung Research
    
 
    
        PSP Element(s)
        G-501600-001
    
 
    
        Grants
        German Center for Infection Research (DZIF, partner site Munich)
The "Bundesministerium fur Bildung und Forschung" of the German Government
    
 
    
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        Erfassungsdatum
        2024-09-27