Orthopoxvirus F13 protein (F13)

The Orthopoxvirus F13 protein, also known as p37 or F13L, is a highly conserved 37 kDa peripheral membrane protein that is essential for the production of extracellular enveloped virus (EEV). It is a member of the phospholipase D (PLD) superfamily and localizes to the trans-Golgi network and late endosomes, where it facilitates the wrapping of intracellular mature virus (IMV) particles with host-derived membranes. This wrapping process is a critical step in the viral life cycle, as EEV is the form of the virus responsible for efficient cell-to-cell spread and long-range dissemination within the host. F13 is the primary molecular target of the antiviral drug Tecovirimat (TPOXX), which binds to a conserved pocket within the protein to inhibit its function. By blocking F13, the drug effectively traps the virus within the primary infected cell, preventing the systemic spread of orthopoxvirus infections such as smallpox (Variola virus) and Mpox. Resistance to treatment can occur through single amino acid substitutions in the F13L gene, which can significantly reduce the binding affinity of inhibitors.

Other names

p37F13LMajor envelope proteinPhospholipase D-like proteinVP37Orthopoxvirus F13 homodimer interfaceVaccinia virus F13 protein

Inhibition of the F13 protein prevents the wrapping of intracellular mature virus (IMV) into extracellular enveloped virus (EEV), thereby blocking viral egress and cell-to-cell spread.