The Marburg virus, a rare, but serious filovirus virus, is a zoonotic virus in which outbreaks are frequently triggered by interaction with the African fruit bat, Rousettus aegyptiacus.
Investigators from The Scripps Research Institute (TSRI) have found more definitive proof that an antibody called MR191 can neutralize the Marburg virus.
The Marburg virus, a rare, but serious filovirus virus, is a zoonotic virus in which outbreaks are frequently triggered by interaction with the African fruit bat, Rousettus aegyptiacus. The infection, which causes fever, chills, headache, and myalgia, can progress to a maculopapular rash, vomiting, diarrhea, and eventually shock and multi-organ failure. Uganda was recently struck with an outbreak of the virus, and while the World Health Organization declared the outbreak to be officially over on December 8, 2017, a total of 3 people died because of the infection.
Scientists have already determined that Marburg has the same pandemic potential as another filovirus, Ebola; however, they also found that the antibody MR191 is able to neutralize the virus. Until now, though, they were not sure exactly how this was done.
As detailed in a study published in Cell Host & Microbe, after creating a map of the structure of the Marburg virus, investigators used x-ray crystallography to reveal that “MR191 neutralizes the virus by mimicking the host receptor and plugging into a spot on the viral surface called the receptor binding site. With this site occupied, the virus can no longer attach itself to human cells and spread infection.” Furthermore, when studying the architecture of the antibody, the investigators were able to determine some important ways that Marburg differs from Ebola. For example, the viral structure of Marburg contains a “wing that sticks out of the side. The wing was particularly important for researchers to map since it appears to be one of only two known sites where protective human antibodies can bind … [U]nlike the wing on Ebola virus, Marburg's wing folds around the outside of the glycoprotein spike,” according to a press release on the study.
Speaking on the ramifications of this discovery in the press release, Erica Ollmann Saphire, PhD, a TSRI professor and senior author of the study stated, “That finding and others in this structure tell us that Marburg is constructed differently from its cousin, the Ebola virus. That means the therapeutic strategy for one may need to be different from the other.”
The investigators also found that both viruses “use a structure called a glycan cap to shield the vulnerable receptor binding site from the human immune system; [however,] the new study reveals that MR191 can get around the glycan cap on Marburg virus—an ability scientists have not observed for any antibodies against Ebola virus.”
Next steps for the research team include studying mutations in the Marburg virus to learn how those mutations can dodge antibodies like MR191 and developing second-line treatments. According to the press release, Dr. Ollmann Saphire and her team hope that clinical trials testing the effectiveness of MR191 will be developed. In fact, Vanderbilt University has since licenses MR191 to a commercial partner.