Orthopoxvirus F13L protein (F13L)

The Orthopoxvirus F13L protein, also known as p37, is a highly conserved peripheral membrane protein essential for the production of extracellular enveloped virus (EEV) in orthopoxviruses such as Variola virus and Monkeypox virus (UniProt P01124; PMID: 15767444). It is located on the surface of the intracellular mature virus (IMV) and plays a critical role in the wrapping process, where IMVs are enclosed in Golgi-derived or endosomal membranes to become intracellular enveloped viruses (IEV) (PMID: 18321971). This process is vital for the efficient spread of the virus from cell to cell and throughout the host organism, as EEV is the form responsible for long-range dissemination (PMID: 11832465). F13L contains motifs similar to the phospholipase D (PLD) superfamily, which are necessary for its function in membrane remodeling during viral egress (PMID: 30044935). Because of its indispensable role in the viral life cycle and its high conservation across the Orthopoxvirus genus, F13L is a primary therapeutic target. The antiviral drug Tecovirimat (TPOXX) specifically targets F13L, inhibiting the formation of EEV and effectively trapping the virus within the host cell (FDA TPOXX Label; CDC Tecovirimat Guidance). This mechanism significantly reduces viral dissemination and is used to treat severe infections including smallpox and mpox.

Other names

Major envelope antigenp37VP37F13L gene productPhospholipase D-like proteinEnvelope protein F13

Tecovirimat inhibits the activity of the F13L protein, which is essential for the wrapping of intracellular mature virus (IMV) with host-derived membranes to form extracellular enveloped virus (EEV). 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.