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Synthetic Fab bound to Marburg virus VP35 interferon inhibitory domainSynthetic Fab bound to Marburg virus VP35 interferon inhibitory domain
Structural highlights
FunctionVP35_MABVP Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Publication Abstract from PubMedMarburg virus causes sporadic outbreaks of severe hemorrhagic fever with high case fatality rates. Approved, effective, and safe therapeutic or prophylactic countermeasures are lacking. To address this, we used phage display to engineer a synthetic antibody, sFab H3, which binds the Marburg virus VP35 protein (mVP35). mVP35 is a critical cofactor of the viral replication complex and a viral immune antagonist. sFab H3 displayed high specificity for mVP35 and not for the closely related Ebola virus VP35. sFab H3 inhibited viral RNA synthesis in a minigenome assay, suggesting its potential use as an antiviral. We characterized sFab H3 by a combination of biophysical and biochemical methods, and a crystal structure of the complex solved to 1.7 A resolution defined the molecular interface between sFab H3 and mVP35 interferon inhibitory domain. Our study identifies mVP35 as a therapeutic target using an approach that provides a framework for generating engineered Fabs targeting other viral proteins. Marburg virus RNA synthesis is inhibited by a synthetic anti-VP35 antibody.,Amatya P, Wagner N, Chen G, Luthra P, Shi L, Borek D, Pavlenco A, Rohrs HW, Basler CF, Sidhu SS, Gross ML, Leung DW ACS Infect Dis. 2019 May 23. doi: 10.1021/acsinfecdis.9b00091. PMID:31120240[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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