Vaccinia virus L1 protein (L1R) (L1R)

Vaccinia virus L1 protein (encoded by the L1R gene) is a 23-29 kDa myristoylated envelope protein that is highly conserved across the Orthopoxvirus genus [1, 3]. It is a critical component of the viral entry/fusion complex (EFC), which is essential for the fusion of the viral membrane with the host cell membrane and the subsequent release of the viral core into the cytoplasm [4, 5]. L1 is expressed on the surface of the intracellular mature virus (IMV) and is a major target for potent neutralizing antibodies, making it a key candidate for subunit and DNA-based vaccines, such as the 4pox vaccine [1, 7, 8]. Research indicates that L1 binds to host cell surfaces independently of glycosaminoglycans, potentially interacting with specific protein receptors to facilitate entry [7, 12]. While no small-molecule inhibitors are currently approved specifically for L1, its structure reveals a hydrophobic cavity that could be targeted for drug design [3, 8]. It remains a primary focus for the development of next-generation poxvirus therapeutics and vaccines designed to prevent infection by variola (smallpox) and monkeypox viruses [3,}