Envelope phospholipase F13 (F13)

Envelope phospholipase F13 (commonly referred to as the F13L protein or P37 protein) is a highly conserved and essential envelope protein encoded by the F13L gene in vaccinia virus and homologous genes in other orthopoxviruses, including monkeypox. Comprised of 372 amino acids, F13 is palmitoylated and associates with the inner leaflet of the outer membrane in the extracellular enveloped virion (EEV). Its principal function is to mediate the wrapping of intracellular mature virus (IMV) with additional membranes to generate EEV, a form of the virus critical for efficient cell-to-cell and long-range viral spread in the host organism. F13 acts as a viral phospholipase-like enzyme, modifying host and/or viral membranes for virion packaging, release, and facilitating fusion/dissolution events necessary for infection. F13 interacts with host cell proteins, such as Rab9 and TIP47, to promote efficient wrapping and transport, and is required for sensitive, timely fusion and entry of EEV into new host cells. The protein is a validated therapeutic target; tecovirimat (ST-246), the first-in-class small-molecule inhibitor, binds F13 and prevents EEV formation and egress, disrupting viral dissemination without apparent effects on host biology. F13 is absent in human cells, making it an attractive antiviral drug target with minimal off-target risk.

Other names

F13L proteinP37 proteinEnvelope protein F13Palmitoylated EV membrane proteinF13P37K

Inhibition of envelope formation/release of extracellular virion by interfering with F13’s function as a phospholipase or lipid-modifying enzyme. Blocking viral spread by restricting egress from host cells.