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 Food and Drug Administration (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 a mouse model.
NIAID also is supporting the development of antibodies to be used as treatments for MERS-CoV. Key studies examined the role of human neutralizing antibodies in virus evolution and prophylactic and postexposure efficacy, demonstrating the effectiveness of different antibody treatments in in vitro and in vivo models of MERS-CoV infection.
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 the NIAID 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 Preclinical Models of Infectious Disease program.