As our knowledge of the molecular structure of Ebola virus increases, so does our chance of preventing and treating the outbreaks of deadly hemorrhagic fever that it causes. Now, a new crystallography study from the US shows how a key Ebola protein – important for virus replication – could be a target for new drugs.

According to the World Health Organization (WHO), as of September 7th, the 2014 outbreak of Ebola virus disease in West Africa has claimed over 2,200 lives. The outbreak, which began in Guinea, has spread to Liberia, Nigeria, Senegal and Sierra Leone.

There is also another Ebola virus disease outbreak in the Democratic Republic of Congo (DRC), which WHO say is a distinct and independent event, involving Ebola strains not derived from the ones currently circulating in West Africa.

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The researchers discovered that the Ebola nucleoprotein has a previously unknown tertiary fold, further examination of which may reveal how the virus assembles itself in infected cells.

In this new study, published in the journal Acta Crystallographica Section D, researchers from the University of Virginia (UVA) used crystallography to obtain the structure of a key protein of the Zaire strain of Ebola virus – the strain circulating in DRC.

Viruses are highly diverse entities – they have a much larger range of genomic structures than animals, plants and bacteria. Their proteins can be encoded in DNA, RNA or both, and the structures of these and how they operate also varies widely.

Like many of its relatives, the Ebola virus has a negative-sense, single-stranded RNA that encodes seven different proteins. One of these proteins is the nucleoprotein and is of interest because it interacts with the viral genome.

Scientists have managed to determine the atomic structure of five of the seven Ebola proteins – nucleoprotein is not one of them, although nucleoproteins from other viruses have been analyzed.

For the study, the researchers engineered a form of E. coli to produce the Ebola nucleoprotein. This allowed them to crystallize and determine the atomic structure of the protein’s “C-terminal domain,” which spans a location they identify as amino-acid “residues 641 to 739.”

There is keen interest in this part of the protein because evidence suggests it is involved in transcribing the genetic instructions for the virus to assemble itself inside host cells.

Using X-ray crystallography, the UVA team, led by virologist Dr. Dan Engel and structural biologist Dr. Zygmunt Derewenda, found that the Ebola nucleoprotein has a previously unknown tertiary fold, further examination of which may well reveal precisely how the virus assembles itself in infected cells.

They believe the structural details they have discovered about this part of the protein could lead to new anti-viral drugs that stop Ebola infection in humans, as Dr. Derewenda explains:

The structure is unique in the RNA virus world. It is not found in viruses that cause influenza, rabies or other diseases.”

This study is an example of researching ways to fight a virus by looking for targets in the virus itself. However, the severity of a viral infection is not only due to the virus, but also to the immune system’s response.

In July 2014, researchers led by the University of Washington in Seattle suggested tackling the immune response to the influenza virus might be a better way to reduce illness severity. Using mice, they looked for genes that are turned on by avian flu.