When MERS-CoV emerged in 2012, NIAID scientists and grantees mobilized quickly to research the virus. Key areas of investigation include basic research on where MERS-CoV comes from and how it causes disease, the development of animal models to study the virus, and the development of treatments and vaccines.
To this end, NIAID hosted a one-day meeting for scientists researching MERS-CoV in June 2013. Discussion focused on the basic and clinical data needed to develop therapeutics and vaccines, lessons learned from the 2003 outbreak of severe acute respiratory syndrome (SARS), and recommendations for next steps. A report of the meeting (PDF), outlining the current state of the science and research goals, was released in September 2013. Priority research areas identified by the workshop include basic research, viral emergence and evolution, surveillance studies, diagnostics, and therapeutics.
Since the meeting, NIAID and others have continued to investigate and respond to the global situation. In May 2014, the Centers for Disease Control and Prevention (CDC) announced the first imported cases of MERS-CoV in the United States. These cases are considered at low risk to the general public because most MERS-CoV transmission to date has occurred through close contact with infected individuals, and there has been no sustained human-to-human spread.
NIAID also leads an interagency working group on MERS-CoV therapeutics. Other federal government agencies represented include CDC, the Food and Drug Administration (FDA), the U.S. Department of Defense, and the Biomedical Advanced Research and Development Authority.
To develop effective therapeutics and vaccines against MERS-CoV, scientists must first understand how the virus survives, infects, and causes disease in people. This knowledge is gained by first studying the virus in tissue culture and then developing animal models that mimic human disease. After studies showed that MERS-CoV does not cause disease in standard mice or hamsters, scientists at NIAID Rocky Mountain Laboratories (RML) took the unusual step of moving directly to developing a large-animal model because of the public health implications posed by MERS.
Their model of MERS-CoV infection in rhesus macaques shows that clinical signs of disease appear within 24 hours of infection, and the virus causes disease deep within the lungs, leading to pneumonia. The RML team is using the model to study how MERS-CoV causes disease and to evaluate potential vaccines and treatments. NIAID-funded researchers have now established a model of infection in mice, and researchers at NIAID and elsewhere continue to try to develop a small-animal study model in rodents and rabbits, which are simpler to use and less expensive than macaques.
NIAID-funded investigators also are working to express, screen, catalog, and biochemically characterize novel MERS-CoV genes to identify new immune pathways related to viral replication and the host defense against MERS-CoV.
Coronaviruses evolve quickly and have a long history of shifting between animal species, leading scientists to explore where MERS-CoV comes from and how people become infected. Thus far, evidence suggests that the virus can be transmitted from person to person but only between people in close contact with one another, such as family members or patients being treated in clinical settings.
Researchers also are investigating whether people are becoming infected through contact with an animal, such as a bat, that acts as a reservoir or carrier for the virus. There also is anecdotal evidence of MERS-CoV patients’ exposure to camels prior to illness. In September 2013, scientists supported by NIAID Centers of Excellence for Influenza Research and Surveillance developed a laboratory test to detect antibodies to a key MERS-CoV protein based on a form of HIV that cannot cause illness. They used this assay to test for MERS antibodies in dromedary camels, water buffalo, pigs, cows, sheep, and goats in Egypt. More than 90 percent of camels tested positive for these antibodies, while all of the other animals tested negative, suggesting that MERS-CoV or a related virus had infected dromedary camels. NIAID scientists also are exploring the possibility of foodborne transmission of MERS-CoV, which is the potential for humans to become infected by eating meat or drinking unpasteurized milk contaminated with the virus.
NIAID-funded researchers at the University of Washington are searching for MERS-CoV therapeutics by analyzing which human genes are significantly disrupted in the early and late stages of infection. This information will help scientists to predict which classes of drugs may be able to stop the virus or the genetic disruptions it causes during infection. Their findings, published in April 2013, show that SARS-CoV and MERS-CoV affect human cells differently. In general, MERS-CoV disrupts more genes more profoundly and at more time points after infection than SARS-CoV.
RML scientists studying MERS-CoV found that a combination of two licensed antiviral drugs, ribavirin and interferon-alpha 2b, can prevent the virus from reproducing in laboratory-grown monkey cells. They subsequently demonstrated in a monkey disease model that the combination of antivirals reduces MERS-CoV replication and improves clinical outcome. Ribavirin and interferon-alpha 2b are routinely used to treat viral infections such as hepatitis C.
NIAID scientists and collaborators also are screening other FDA-approved drugs to address the need for effective treatments. Scientists have identified 27 drugs that, in test tube experiments, showed activity against both MERS-CoV and SARS-CoV. The research team is now studying the effects of some of the identified compounds in the mouse model.
Scientists have learned that for MERS-CoV to infect a person, the virus enters cells using a protein known as the spike, or S protein. After entering the cell, the virus delays the normal immune system response, allowing the infection to gain a foothold in the body. By the time the immune system recovers, the infection has progressed and become much harder to fight off. NIAID-funded scientists are exploring MERS-CoV vaccines that would block the S protein or the delay of the immune system. Other grantees are working to develop a live, attenuated MERS-CoV vaccine, which is a type of vaccine that contains a version of the living microbe that has been weakened in the lab, so it cannot cause disease. Investigators at NIAID’s Vaccine Research Center are using techniques learned from SARS-CoV vaccine development to create a MERS-CoV DNA vaccine with plans to test in mice.
In August 2013, NIAID awarded two contracts to advance research into new treatments and vaccines for MERS-CoV through its Animal Models of Infectious Disease program.
Last Updated February 06, 2015
Last Reviewed October 28, 2013