Project period: 2019 - 2020
Project leader: Dariusz Plewczyński
Centre of New Technologies, University of Warsaw
Ebolavirus and Marburgvirus (hencefore denoted EBOV and MARV, respectively) are two genera of the negative sense RNA virus family Filoviridae, order mononegavirales. Filoviruses cause rare but fatal viral hemorrhagic fevers-VHF in equatorial Africa–with potential for regional and international urban spread. Both viruses associated VHFs present with a similar prodrome; mimicking several tropical infectious diseases. Early detection is important for mobilizing swift response and control. Existing technologies for filovirus detection are not suited for point of care (POC) use, being expensive, not fast-enough and requiring laboratory facilities absent in many villages where index cases occur. While two rapid diagnostic tests (RDTs) have recently emerged detecting EBOV at the point of care (POC), there are no pan-filovirus targeted RDTs.
We hyphothesize that the post translational modifications of EBOV glycoproptein (GP) mask target epitopes from detection by mAbs. Therefore the overall goal of this project is to develop biochemical treatments that adjust native EBOV GP in patient sample as a target for rapid diagnostic testing.
We performed the in silico study of the 3D crystal structure of filovirus glycoprotein (GP). The analysis allowed us to establish the complete structural map of post-translational modifications, including glycosylation, for this protein. This revealed the role of such changes in modulating the interactions between the GP and antibodies.