@article{You2026, 
author = {Yu You and Fanli Yang and Sheng Lin and Zimin Chen and Siqi Shu and Yueru Yu and Bin He and Yu Cao and Guangwen Lu},
title = {Rabies virus glycoprotein: Structure, function, and antivirals},
year = {2026},
journal = {hLife},
volume = {4},
number = {2},
pages = {67-86},
keywords = {structural features, rabies virus, glycoprotein, antivirals, entry and infection},
url = {https://www.sciopen.com/article/10.1016/j.hlife.2025.06.003},
doi = {10.1016/j.hlife.2025.06.003},
abstract = {Rabies, a persistent and historic global zoonosis, continues to impose a significant public health burden, particularly in resource-limited regions. The causative agent, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae), possesses a surface glycoprotein (G) that is pivotal for virus entry and pathogenesis. Rabies virus glycoprotein (RABV-G) mediates binding to host cell receptor(s) and acidic-pH-dependent membrane fusion, enabling the release of RNA genome into the host cytoplasm. It is also the main target for neutralizing antibodies and the major component of rabies vaccines. In this review, we systematically summarize the structural features, functional mechanisms, and antiviral targeting strategies of RABV-G, emphasizing recent structural insights into its conformational dynamics. Key neutralizing epitopes and their recognition by monoclonal antibodies are discussed, along with antiviral strategies, including entry inhibitors, antibody therapies, and advanced vaccine platforms. Accumulating structural analyses indicate that the pH-dependent and reversible conformational transitions of this class Ⅲ viral fusion protein underlie both viral infectivity and vulnerability to immune intervention. Collectively, available data establish that neutralizing epitopes on RABV-G are conformationally defined and dynamically regulated during fusion, thereby constraining viral entry and dictating the effectiveness of antibody- and entry inhibitor–mediated neutralization. Together, these findings establish RABV-G as the primary determinant of rabies virus virulence and immune control. By exploring the structural framework and prospective treatment modalities, we aim to enhance our understanding of rabies virus, particularly the glycoprotein G, and support ongoing initiatives to alleviate the burden of rabies, offering renewed optimism in the battle against this formidable infectious disease.}
}