Variola virus protein L1 (L1)

Variola virus protein L1 (encoded by the L1R gene) is a highly conserved, myristoylated envelope protein essential for the life cycle of the smallpox virus [1, 2]. It is a key component of the Entry Fusion Complex (EFC), which mediates the fusion of the viral envelope with the host cell membrane, allowing the viral core to enter the cytoplasm [18, 19]. L1 also plays a critical role in virion assembly; its N-terminal myristoylation is required for the maturation of infectious intracellular mature virions (IMVs) [1, 5]. Because of its vital role in entry and assembly, L1 is a primary target for potent neutralizing antibodies and is a major component of modern subunit and DNA vaccines against orthopoxviruses [5, 20]. While current FDA-approved antivirals like tecovirimat target other viral proteins, L1 remains a high-priority target for the development of next-generation therapeutics and vaccines to protect against smallpox and related zoonotic poxviruses [4, 7].

Other names

L1R proteinM1R proteinIMV membrane proteinVirion membrane protein M25Myristoylated envelope protein L1

Neutralization of viral entry and membrane fusion; inhibition of virion assembly by blocking the myristate-binding hydrophobic cavity.