Revolutionary Nanobody Breakthrough: Targeting the Ebola Virus with Precision

Structural Basis for the Anti-EBOV Functions of Nanosota-EB1. (A) Cryo-EM structure of EBOV GP-ΔM complexed with Nanosota-EB1 (top view; surface presentation). The three subunits of EBOV GP-ΔM are colored orange, gray, and green, respectively. Nanosota-EB1 is displayed in blue. The trimeric GP-ΔM is engaged by two Nanosota-EB1 molecules. (B) Cryo-EM structure of EBOV GP-ΔM complexed with Nanosota-EB1 (side view). The overall design is presented in surface presentation, with one GP subunit and one Nanosota-EB1 molecule depicted in cartoon presentation. Nanosota-EB1 binds to the glycan cap of EBOV GP. The glycan cap is shown in cyan. The cathepsin cleavage site adjacent to the glycan cap is highlighted with a red circle. (C) The interaction interface between Nanosota-EB1 and the glycan cap. Nanosota-EB1 attaches to the β17 strand of the glycan cap, displacing the β18 strand and moving it to form a loop. Credit: PLOS Pathogens (2024). DOI: 10.1371/journal.ppat.1012817

The Ebola virus, recognized as one of the most lethal pathogens, incurs a mortality rate of approximately 50%, presenting a significant risk to global health and safety. In response to this issue, researchers at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center have established the first nanobody-based inhibitors aimed at combating the Ebola virus.

This research has been published in the journal PLOS Pathogens.

Nanobodies are minuscule antibodies sourced from animals such as alpacas. Their diminutive size enables them to access regions of the virus and human tissues that larger antibodies are unable to reach. During the COVID-19 pandemic, the team engineered nine nanobodies to combat the virus. They have now utilized this technology to create two additional nanobody inhibitors for Ebola: Nanosota-EB1 and Nanosota-EB2.

The nanobodies operate through different mechanisms to hinder the Ebola virus. The virus conceals the portion it utilizes for attachment to human cells beneath a protective covering. Nanosota-EB1 obstructs this layer from opening, thereby preventing the virus from adhering to cells. Conversely, Nanosota-EB2 targets a segment of the virus crucial for infiltrating cells, thereby halting its transmission. In laboratory assessments, Nanosota-EB2 demonstrated notable efficacy, significantly enhancing survival rates in mice infected with Ebola.

These nanobodies symbolize a critical advancement towards treatments for other viruses within the same family, including the Sudan and Marburg viruses. This flexibility is attributed to a newly developed design approach for nanobodies by the research team.

The investigation was spearheaded by Dr. Fang Li, co-director of the Midwest AViDD Center and a professor of Pharmacology. The research group comprised graduate student Fan Bu, research scientist Dr. Gang Ye, research associates Alise Mendoza, Hailey Turner-Hubbard, and Morgan Herbst (Department of Pharmacology), Dr. Bin Liu (Hormel Institute), and Dr. Robert Davey (Boston University).