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The Orthopoxvirus L1 protein, encoded by the L1R gene, is a highly conserved, myristoylated transmembrane protein located on the envelope of the mature virus (MV) particle (UniProt P04302). It plays a critical role in the viral life cycle, specifically mediating the entry and fusion of the virus into host cells (PubMed: 11832551). Because of its essential function and high conservation across species such as Variola (smallpox), Monkeypox (Mpox), and Vaccinia viruses, L1 is a primary target for the development of vaccines and therapeutic antibodies (PubMed: 15956310). Neutralizing antibodies directed against L1, such as the monoclonal antibody 7D11, can prevent infection by blocking the virus's ability to penetrate the host cell membrane (PubMed: 16188995). While small-molecule inhibitors specifically targeting L1 are less common than those targeting other poxvirus proteins like VP37, L1 remains a cornerstone for passive and active immunization strategies. Research indicates that L1-specific antibodies are a major component of the protective immune response elicited by traditional smallpox vaccines (PubMed: 12743285).
Neutralization of viral entry by blocking the fusion of the viral envelope with the host cell membrane.
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