Marburg Virus Entry Mechanism Reveals New Targets for Antivirals and Infection Prevention Strategies

As global health systems continue to prepare for high-consequence pathogens, new research on the Marburg virus is raising urgent questions about its outbreak potential and readiness for infection prevention.

In a recent study, Fang Li, PhD, and his team at the University of Minnesota Medical School uncovered key insights into how the Marburg virus enters human cells, revealing an efficiency that may exceed that of the Ebola virus. These findings deepen scientific understanding of filoviruses and carry immediate implications for infection preventionists, frontline clinicians, and public health systems.

From reinforcing the importance of rapid identification and isolation to informing the development of targeted antivirals and vaccines, the research highlights both vulnerabilities in current preparedness and opportunities for innovation.

In this Q&A with Infection Control Today (ICT), Li discusses the science of viral entry, its implications for outbreak risk, and how health care systems can better prepare for emerging threats.

ICT: Why did you choose to do this study?

Fang Li, PhD: Our long-term goal is to develop antivirals that block viral entry across major virus families with pandemic potential. After studying coronavirus entry mechanisms for decades, we turned to filoviruses as a second major focus. Marburg is an especially important target within the filovirus family because of its high fatality rate and the lack of approved countermeasures. To develop effective entry inhibitors, we first needed to understand exactly how the virus enters human cells.

ICT: Your research suggests the Marburg virus may enter human cells up to 300 times more efficiently than Ebola. What does this tell us about outbreak potential?

FL: Our data suggest that Marburg virus can enter human cells much more efficiently than Ebola, and that is concerning. Based on what we know from coronaviruses, efficient cell entry can contribute to outbreak potential, although immune evasion and other viral factors also matter. Still, outbreak size depends on more than virology alone. The ecology of virus-carrying hosts, in this case bats, influences how spillover occurs, and once the virus infects people, early detection and rapid public health response are critical to limiting person-to-person spread.

ICT: For infection preventionists working in hospitals, what are the most important practical implications of this discovery?

FL: Our findings suggest that Marburg virus may be highly infectious, which reinforces the importance of strict personal protection in hospital settings. Filovirus transmission has often been amplified in health care and funeral settings, so rapid recognition, isolation, and strong infection-control practices are critical. At the same time, these results highlight the need for both preventive and treatment strategies that can block infection early.

ICT: Your team identified a nanobody that can block infection. How does this move the field closer to effective antivirals or preventive therapies?

FL: Our nanobody was able to penetrate the protective cap on the Marburg entry protein and block a site that is essential for receptor binding and infection. This showed that the protective cap is only partially protective, which is an important new finding from our study. Because the virus does not fully shield this critical receptor-binding site, it creates a real vulnerability that therapeutics and vaccines may be able to exploit.

ICT: Was there anything that especially surprised you during the research?

FL: Many of the major findings in this study were surprising to us, including the unusually efficient cell entry, the fact that the protective cap is only partially protective, and the way Marburg binds its receptor in a distinct orientation and with higher affinity. The biggest surprise was the receptor-binding mechanism itself.

ICT: Currently, there are no FDA-approved vaccines or therapeutics for Marburg. Based on your findings, what are the most promising pathways for developing countermeasures?

FL: Our structural insights point to 2 especially promising strategies. The first is to block the interaction between the Marburg entry protein and its receptor using neutralizing antibodies, nanobody-based therapies, small-molecule compounds, or structure-guided vaccines that target the receptor-binding site beneath the leaky protective cap.

The second is to target the shape changes in the entry protein triggered by receptor binding that help the virus break into cells. In that context, stabilizing the entry protein with antibodies, nanobodies, or small-molecule compounds is also a promising strategy. Together, these findings provide a strong foundation for rational countermeasure development.

ICT: From an outbreak-preparedness perspective, does the mechanism you discovered change how public health systems should approach Marburg?

FL: Yes. Because the Marburg virus enters human cells so efficiently, our findings suggest it may have high infectivity. This increases the importance of preparedness measures aimed at stopping transmission early. Rapid recognition, isolation, strict PPE use, and strong infection-control practices are essential, especially because filovirus spread has often been amplified in health care and funeral settings.

ICT: What lessons from Marburg research should hospitals be paying attention to now, even in regions where cases are rare?

FL: Hospitals need to stay prepared for high-consequence pathogens even when cases are rare. That means maintaining strong protocols for rapid identification, isolation, and infection control, along with PPE (personal protection equipment) training and clear response plans, so health systems can respond quickly and effectively when threats emerge.

ICT: Your research was enabled after the (Midwest Antiviral Drug Discovery) AViDD grant was reinstated. How important is sustained federal support for studying emerging pathogens like Marburg?

FL: Sustained federal support is extremely important because research on emerging pathogens must happen before major outbreaks occur, not only during emergencies. We are grateful to the National Institute of Allergy and Infectious Diseases (NIAID) for supporting this work through the Midwest AViDD Center. That support has enabled substantial progress in developing entry inhibitors against coronaviruses and filoviruses, and we hope to extend that expertise to other major virus families with pandemic potential.

One of the clearest lessons from COVID-19 is that we need systematic preparation against virus families with pandemic potential, rather than waiting until a crisis begins. Our goal is to address these threats 1 virus family at a time, and build a stronger foundation for preparedness.