Scientists develop nanobody inhibitors to target deadly Ebola virus

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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 shown in blue. The trimeric GP-ΔM is bound by two Nanosota-EB1 molecules. (B) Cryo-EM structure of EBOV GP-ΔM complexed with Nanosota-EB1 (side view). The overall structure is shown in surface presentation, with one GP subunit and one Nanosota-EB1 molecule shown in cartoon presentation. Nanosota-EB1 binds to the glycan cap of EBOV GP. The glycan cap is colored cyan. The cathepsin cleavage site near the glycan cap is marked by a red circle. (C) The binding interface between Nanosota-EB1 and the glycan cap. Nanosota-EB1 binds to the β17 strand of the glycan cap, displacing the β18 strand and pushing it aside to form a loop. Credit: PLOS Pathogens (2024). DOI: 10.1371/journal.ppat.1012817

Ebola virus, one of the deadliest pathogens, has a fatality rate of about 50%, posing a serious threat to global health and safety. To address this challenge, researchers at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center have developed the first nanobody-based inhibitors targeting the Ebola virus.

The research is published in the journal PLOS Pathogens.

Nanobodies are tiny antibodies derived from animals like alpacas. Their small size allows them to access areas of the virus and human tissues that larger antibodies cannot. During the COVID-19 pandemic, the team created nine nanobodies to fight COVID-19. Now, they've used this technology to develop two new nanobody inhibitors for Ebola: Nanosota-EB1 and Nanosota-EB2.

The nanobodies work in different ways to stop Ebola. The virus hides the part it uses to attach to human cells under a protective layer. Nanosota-EB1 prevents this layer from opening, blocking the virus from attaching to cells. Nanosota-EB2 targets a part of the virus essential for breaking into cells, stopping its spread. In lab tests, Nanosota-EB2 was especially effective, greatly improving survival rates in Ebola-infected mice.

These nanobodies represent a major step toward treatments for other viruses in the same family, like Sudan and Marburg viruses. This adaptability comes from a new nanobody design method recently developed by the team.

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

More information: Fan Bu et al, Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection, PLOS Pathogens (2024). DOI: 10.1371/journal.ppat.1012817

Journal information: PLoS Pathogens

Provided by University of Minnesota Medical School