Marburg Virus's Deadly Efficiency Unlocked: New Insights Pave Way for Antivirals

University of Minnesota researchers have identified that the Marburg virus, known for its high fatality rate of 73%, exhibits unusually efficient entry into human cells. Published in Nature, the study also details structural features within the virus's entry protein that explain this efficiency and suggest a strategy for blocking infection.

Unpacking Marburg's Deadly Efficiency

Researchers developed a controlled system to compare the entry proteins of Marburg and Ebola viruses. This meticulous comparison revealed a striking difference: Marburg's entry protein is up to 300 times more efficient at facilitating viral entry into human cells compared to Ebola's.

Structural Secrets Revealed

While both viruses utilize the same human receptor for cell entry, the study found that Marburg's entry protein binds to this receptor in a distinct orientation and with greater affinity. This enhanced binding also induces specific shape changes within the viral protein that significantly aid the virus in cell entry, contributing to its high infectivity.

Dr. Fang Li, a senior author and professor of pharmacology at the University of Minnesota Medical School, stated that the study establishes a new framework for comparing viral entry efficiency and links structural features to infectivity, providing a roadmap for therapeutic interventions. Dr. Li emphasized that understanding Marburg virus's lethality also reveals a vulnerability for antiviral development.

Discovery of a Blocking Nanobody

The research team also made a significant discovery: a nanobody capable of penetrating a protective cap on Marburg's entry protein. Once inside, this nanobody binds to the protein, preventing its attachment to the human receptor. Laboratory tests confirmed this nanobody's ability to effectively block Marburg virus entry into cells. This finding presents a promising new avenue for antiviral drug development.

Key contributors to the study included assistant professor Gang Ye, graduate student Fan Bu, and associate professor Bin Liu. The National Institute of Allergy and Infectious Diseases, via the Midwest Antiviral Drug Discovery Center, provided essential support for this groundbreaking research.