Track 7: New Lassa Fever Therapy

The deadly Lassa virus is indigenous to West Africa and is mostly spread by rodents. Lassa fever is brought on by the virus; it affects up to 300,000 people a year and often begins with flu-like symptoms before progressing to more serious sickness, death, and long-lasting effects including deafness. The Lassa virus is particularly harmful to expectant mothers since approximately 90% of infections during pregnancy result in death. Glycoproteins are used by Lassa to enter host cells and start an infection. The glycoprotein structure of Hastie provided virologists with an understanding of their opponents. The scientists uncovered precisely how the three antibodies in Arevirumab-3 neutralize the Lassa virus based on the high-resolution structures and several functional experiments.

The area of the glycoprotein is where three molecules (called protomers) come together to form a "trimer," a kind of twisted trefoil, as Hastie describes it. Lassa would normally use this region of the glycoprotein to bind with receptors on host cells, but the latest structure shows how a single 8.9F jumps in and binds to all three protomers simultaneously to block infection. Meanwhile, the neutralizing antibody called 12.1F binds to just one protomer in the three-sided trimer.  12.1F would be abundant in any therapeutic. Each 12.1F antibody can attach to a protomer and move as a trio to help neutralize the virus. The Lassa virus is the target of copies of antibody 37.2D that attach in a way that binds neighboring protomers together. Since the Lassa virus needs to open up its trimer to infect host cells, this antibody activity is a major challenge for the virus. Its entrance mechanism is locked up and impossible to operate with 37.2D on the scene.


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