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"Trojan Horse" Strategy Uses Bispecific Antibodies to Block Ebola from Invading Cells

SEP 20, 2016 | KRISTI ROSA
In a collaborative effort, researchers from Albert Einstein College of Medicine, US Army Medical Research Institute of Infectious Diseases (USAMRIID), Integrated Biotherapeutics, Vanderbilt University Medical Center, and The Scripps Research Institute have discovered what they refer to as a “Trojan Horse” strategy that uses two developed bispecific antibodies that have proved active against all five strains of the Ebolavirus.

Previously known as Ebola hemorrhagic fever, Ebola is a rare, deadly disease that is caused by infection with one of the Ebola virus strains, according to the Centers for Disease Control and Prevention (CDC). First discovered in 1976 near what is now the Democratic Republic of the Congo, Ebolavirus can be found in several African countries. The largest outbreak in Ebola history started in March 2014 and resulted in over 11,000 deaths.

Although monoclonal antibodies are currently the best treatment in the fight against Ebola, there exists at least one major setback: monoclonal antibodies only target one of the Ebolavirus species out of the five known to exist. ZMapp, composed of three different monoclonal antibodies, targets Zaire ebolavirus, one of the most dangerous Ebola virus species, but it fails to deliver protection against the Bundibugyo ebolavirus and Sudan ebolavirus, according to the press release.

This knowledge prompted researchers to discover a different way to combat Ebola, one that could offer protection to a number of the viruses instead of just a single specific one. When developing the monoclonal antibodies, researchers set out to target viruses after they entered the host’s lysosomes, according to the press release.

Filoviruses, such as Ebola, are able to enter cells through the use of glycoproteins that allow the filovirus to attach to the outer membrane of the host cell. Lysosomes are soon created, when part of the cell membrane encompasses the virus and then “pinches off.” By utilizing the resources of the host cell, filoviruses are then able to break out of these lysosomes in an attempt to enter the cell’s cytoplasm. Once there, the filovirus is free to replicate, according to the press release.

However, “Enzymes in the lysosome slice a ‘cap’ from the virus’s glycoproteins, unveiling a site that binds to the NPC1 embedded in the lysosome membrane,” according to the press release. Attaching to the protein, Niemann-Pick C1 (NPC1) is the only opportunity that the Ebola virus has to break out of the lysosome and replicate.

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