Orthopoxvirus F13 envelope protein (F13)

The Orthopoxvirus F13 envelope protein, also known as VP37, is a highly conserved 37-kDa protein that plays a pivotal role in the viral life cycle by mediating the formation of extracellular enveloped virus (EEV) (UniProt: P01124). While the intracellular mature virus (IMV) is the most abundant infectious form, the EEV form is essential for the rapid cell-to-cell and systemic spread of the virus within a host (Yang et al., 2005, J. Virol.). F13 facilitates the wrapping of IMV particles with host-derived membranes from the trans-Golgi network or endosomes. This protein is the specific molecular target of Tecovirimat (TPOXX), an antiviral medication approved for the treatment of smallpox and used for Mpox (FDA: TPOXX Label). By binding to F13, Tecovirimat prevents the wrapping process and subsequent viral egress, effectively halting the progression of the disease (Grosenbach et al., 2018, NEJM). Because F13 is highly conserved across the Orthopoxvirus genus, including Variola, Monkeypox, and Vaccinia viruses, it serves as a robust target for broad-spectrum orthopoxvirus therapeutics.

Other names

VP37p37F13L proteinMajor envelope protein VP37Phospholipase D-like protein

Tecovirimat inhibits the activity of the Orthopoxvirus F13 protein, which is required for the wrapping of intracellular mature virus (IMV) with a second lipid bilayer to form extracellular enveloped virus (EEV) (FDA: TPOXX Label). By blocking this step, the drug prevents the egress of the virus from the infected cell, thereby limiting the spread of the infection within the host (Grosenbach et al., 2018, NEJM).