Orthopoxvirus VP37 envelope wrapping protein (VP37) (VP37)

The Orthopoxvirus VP37 protein, encoded by the F13L gene, is a highly conserved 37-kDa membrane protein essential for the production of extracellular enveloped virus (EEV) (UniProt: P01124). It plays a critical role in the viral life cycle by mediating the wrapping of intracellular mature virus (IMV) with host-derived Golgi or endosomal membranes to form intracellular enveloped virus (IEV) (PubMed: 15919924). This process is vital for viral egress and the subsequent spread of the virus throughout the host organism. Tecovirimat (TPOXX) targets VP37, effectively trapping the virus within the infected cell and preventing the systemic dissemination of the pathogen (FDA: TPOXX Label). This target is highly conserved across the Orthopoxvirus genus, making it a robust focal point for broad-spectrum antiviral therapy against smallpox, mpox, and cowpox (PubMed: 29996044). Because VP37 has no human homolog, it offers a high degree of selectivity for antiviral intervention with a favorable safety profile for the host.

Other names

F13L proteinp37Major envelope proteinEnvelope wrapping proteinF13Orthopoxvirus F13 protein

Tecovirimat acts as a potent inhibitor of the Orthopoxvirus VP37 protein. It binds to VP37 and disrupts its interaction with host cellular proteins, such as Rab9 and TIP47, which are required for the wrapping of the virus in a secondary envelope (PubMed: 19158241). By blocking this wrapping step, tecovirimat prevents the conversion of intracellular mature virus (IMV) into extracellular enveloped virus (EEV), thereby inhibiting viral release and cell-to-cell spread (PubChem: CID 16124778).