Structural basis of anti-EBOV function of Nanosota-EB1. (A) Cryo-EM structure of EBOV GP-ΔM in complex with Nanosota-EB1 (top view, surface view). The three subunits of EBOV GP-ΔM are colored orange, gray, and green, respectively. Nanosota-EB1 is shown in blue. Two Nanosota-EB1 molecules are bound to the trimeric GP-ΔM. (B) Cryo-EM structure (side view) of EBOV GP-ΔM in complex with Nanosota-EB1. The overall structure is shown in surface representation, with one GP subunit and one Nanosota-EB1 molecule shown in cartoon representation. Nanosota-EB1 binds to the glycan cap of EBOV GP. The glycan cap is cyan in color. The cathepsin cleavage site near the glycan cap is marked with a red circle. (C) Binding interface between Nanosota-EB1 and glycan cap. Nanosota-EB1 binds to the β17 strand of the glycan cap, displacing and displacing the β18 strand to form a loop. Credit: PLOS Pathogens (2024). DOI: 10.1371/journal.ppat.1012817
Ebola virus is one of the most deadly pathogens, with a case fatality rate of approximately 50%, posing a serious threat to global health and security. To address this challenge, researchers at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center have developed the first nanobody-based inhibitor to target the Ebola virus.
The study is published in the journal PLOS Pathogens.
Nanobodies are small antibodies derived from animals such as alpacas. Their small size allows them to access areas of viruses and human tissue that are inaccessible to larger antibodies. During the COVID-19 pandemic, the team created nine nanobodies to fight COVID-19. Now, they have used this technology to develop two new nanobody inhibitors against Ebola, Nanosota-EB1 and Nanosota-EB2.
Nanobodies work in a variety of 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 parts of the virus that are essential for entry into cells, stopping the virus from spreading. In clinical tests, Nanosota-EB2 was particularly effective, significantly improving survival in mice infected with Ebola.
These nanobodies represent a major step toward treating other viruses in the same family, such as Sudan virus and Marburg virus. 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 professor of pharmacology. The research team included graduate student Fan Bu, research scientist Dr. Gang Ye, research assistants Alise Mendoza, Hailey Turner-Hubbard, Morgan Herbst (Department of Pharmacology), Dr. Bin Liu (Hormel Institute), and Dr. Robert Davey. (Boston University).
Further 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
Provided by University of Minnesota School of Medicine
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