Scientists discover workings of first promising Marburg virus treatment

January 10, 2018, The Scripps Research Institute
An antibody called MR191 can neutralize the deadly Marburg virus. Credit: Ollmann Saphire Lab

With a mortality rate of up to 88 percent, Marburg virus can rip through a community in days. In 2005, an outbreak of Marburg virus struck a pediatric ward in the country of Angola. With no treatment available, doctors struggled to help as the virus killed 329 of 374 infected patients.

Now, scientists at The Scripps Research Institute (TSRI) have discovered the workings of the first promising treatment for Marburg virus, a pathogen with the same pandemic potential as Ebola virus. The research builds on previous studies showing that an antibody called MR191 can neutralize Marburg—though no one knew exactly how it targeted the virus.

For the new study, TSRI scientists created a map of the virus' structure and revealed through high-resolution imaging how MR191 targets and neutralizes the virus. This antibody—or a strategy to elicit this antibody in patients—could finally give doctors a way to successfully treat the disease.

"This is the first antibody therapeutic found that could treat Marburg," says Erica Ollmann Saphire, PhD, a TSRI professor and senior author of the study, published today in the journal Cell Host & Microbe.

"With this new structure, we can start to see how this treatment works," adds Liam King, a TSRI graduate student and first author of the study. "We have also learned new things about the virus itself that could lead to new treatments and vaccines."

The scientists used a technique called x-ray crystallography and found 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.

TSRI Graduate Student Liam King and Professor Erica Ollmann Saphire, PhD. Credit: Madeline McCurry-Schmidt / The Scripps Research Institute

The imaging also shows part of the architecture of a "wing" that sticks out of the side of the viral structure. 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.

As researchers draw up the battle plans against Marburg virus, they are noticing important ways Marburg differs from its close relative, Ebola virus. The new study reveals that, unlike the wing on Ebola virus, Marburg's wing folds around the outside of the glycoprotein spike.

"That finding and others in this structure tell us that Marburg is constructed differently from its cousin, the Ebola virus," says Ollmann Saphire. "That means the therapeutic strategy for one may need to be different from the other."

Another key difference: While both viruses use a structure called a glycan cap to shield the vulnerable receptor binding site from the human immune system, 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 .

Ollmann Saphire says the next step is to study how known mutations in Marburg evade such and to use that information to devise second-line treatments. Soon, the team hopes to see the antibody therapeutic go into clinical trials. As part of this effort, study collaborators at Vanderbilt University have licensed MR191 to a commercial partner.

Explore further: Researchers find new antibody weapons against Marburg virus

More information: "The Marburg virus-neutralizing human monoclonal antibody MR191 targets a conserved site to block virus receptor binding," Cell Host & Microbe (2018).

Related Stories

Researchers find new antibody weapons against Marburg virus

June 29, 2015
A new study led by scientists at The Scripps Research Institute (TSRI) identifies new immune molecules that protect against deadly Marburg virus, a relative of Ebola virus. The research provides ingredients needed to develop ...

Researchers inhibit Ebola virus

December 29, 2017
The incurable Ebola virus has long been feared due to its high mortality rate and danger of infection. Now researchers from the University of Copenhagen and Phillips Universität Marburg have succeeded in inhibiting the virus ...

Ebola-like Marburg virus kills two in Uganda: official

October 19, 2017
Two people have died from the Marburg virus in eastern Uganda, in the country's first outbreak of the deadly Ebola-like pathogen in three years, the health ministry said Thursday.

Uganda declares itself free of Ebola-like Marburg virus

November 11, 2014
Ugandan health officials on Tuesday declared the country free of the Ebola-like Marburg virus after completing a 42-day surveillance period under World Health Organization (WHO) rules.

Uganda Marburg virus outbreak is contained: WHO (Update)

December 8, 2017
Uganda has contained an outbreak of the Ebola-like Marburg virus weeks after it emerged, the World Health Organization said Friday, praising improved response systems since the disastrous West African Ebola epidemic.

Recommended for you

Polio: Environmental monitoring will be key as world reaches global eradication

October 15, 2018
Robust environmental monitoring should be used as the world approaches global eradication of polio, say University of Michigan researchers who recently studied the epidemiology of the 2013 silent polio outbreak in Rahat, ...

Study traces hospital-acquired bloodstream infections to patients' own bodies

October 15, 2018
The most common source of a bloodstream infection acquired during a hospital stay is not a nurse's or doctor's dirty hands, or another patient's sneeze or visitor's cough, but the patient's own gut, Stanford University School ...

Researchers make essential imaging tests safer for people at risk of acute kidney injury

October 15, 2018
Every year, millions of people undergo medical tests and procedures, such as coronary angiography, which use intravascular contrast dyes. "For the majority of patients, these are safe and necessary procedures. However, about ...

Medical marijuana might help MS patients, but uncertainty remains

October 13, 2018
Medical products derived from marijuana might have a mild benefit in treating symptoms of multiple sclerosis, based on reports from patients.

Do not give decongestants to young children for common cold symptoms, say experts

October 11, 2018
Decongestants should not be given to children under 6—and given with caution in children under 12—as there is no evidence that they alleviate symptoms such as a blocked or runny nose, and their safety is unclear, say ...

New techniques can detect Lyme disease weeks before current tests

October 11, 2018
Researchers have developed techniques to detect Lyme disease bacteria weeks sooner than current tests, allowing patients to start treatment earlier.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.