#Marburg virus #RNA #synthesis is inhibited by a synthetic anti-VP35 #antibody (ACS Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

ACS Infect Dis. 2019 May 23. doi: 10.1021/acsinfecdis.9b00091. [Epub ahead of print]

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.

 

Abstract

Marburg 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 Å 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.

PMID: 31120240 DOI: 10.1021/acsinfecdis.9b00091

Keywords: Marburg virus; Monoclonal antibodies.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.