Sudan virus VP40 matrix protein (SUDV VP40)

The Sudan virus VP40 matrix protein is the most abundant structural protein of the Sudan ebolavirus (SUDV) and is essential for the viral life cycle. It drives the assembly and budding of new virions from the plasma membrane of infected host cells by recruiting host endosomal sorting complex required for transport (ESCRT) machinery through its late (L) domain motifs, such as PTAP and PPEY [1, 2]. VP40 exhibits significant structural plasticity, adopting different oligomeric states to perform distinct functions: it forms dimers for transport to the cell membrane, hexamers to build the viral matrix, and octameric rings to regulate viral RNA transcription [3, 4]. Because it is critical for viral replication and lacks a direct human homolog, it is considered a prime therapeutic target for Sudan virus disease [4]. Current research focuses on small molecules or peptide mimetics that can prevent the assembly of these functional oligomers or disrupt essential interactions with host proteins [5]. As a target, it offers the potential to arrest the spread of the virus within the host by preventing the release of infectious particles [6]. Sources: [1] UniProt (P35260): Matrix protein VP40 - Sudan ebolavirus (strain Gulu). [2] Harty, R. N., et al. (2000). "A PPxY motif within the VP40 protein of Ebola virus interacts with NEDD4 and facilitates virus budding." PNAS. [3] Bornholdt, Z. A., et al. (2013). "Structural rearrangement of ebola virus VP40 begets multiple functions in the virus life cycle." Cell. [4] Suder, E. L., et al. (2018). "Ebola Virus Matrix Protein VP40: Therapeutic Target and Tool for Biomedical Research." Life. [5] Han, Z., et al. (2021). "Small-molecule inhibitors of Ebola virus VP40-host interactions." Journal of Virology. [6] Stahelin, R. V. (2014). "Membrane binding and bending in the Ebola virus life cycle." Frontiers in Microbiology.

Other names

Matrix protein VP40SUDV matrix proteinSudan ebolavirus matrix protein VP40VP40

Inhibition of viral budding and assembly by disrupting VP40 oligomerization or blocking the interaction between the viral L-domain and host ESCRT machinery proteins like TSG101 or NEDD4.