Researchers at Cornell University in Ithaca, NY, suggest blocking an enzyme that helps the MERS virus enter host cells may lead to treatments for the recently identified and deadly respiratory virus.

Middle East respiratory syndrome coronavirus (MERS-CoV), is a member of the coronavirus family which in humans causes illnesses ranging from the common cold to severe acute respiratory syndrome (SARS).

According to the World Health Organization (WHO), MERS was first identified in Saudi Arabia in 2012, and both the virus and the disease it causes are continuing to evolve.

Similar to other viruses known as enveloped viruses, coronaviruses enter host cells by fusing with their cell membranes. Once inside, they use the host cells’ resources to make copies of themselves, escape and infect further cells.

Membrane fusion in coronaviruses is facilitated by a spike protein that is activated by a protease enzyme at a location known as a cleavage site.

illustration of the mers virusShare on Pinterest
Prof. Whittaker and Dr. Millet suspect the MERS-CoV strain that infects humans mutated about 2.5 years ago from a strain in camels.

Writing in the Proceedings of the National Academy of Sciences, the Cornell researchers describe how they discovered a protease called furin activates the fusion process in the MERS virus at two cleavage sites. The study is thought to be the first to describe a natural coronavirus with a spike protein containing two furin cleavage sites.

Study authors Gary Whittaker, professor of virology, and Jean Millet, a postdoctoral associate in his lab, suggest the extra cleavage site in the MERS virus spike might be what allows the virus to spread more in the human or animal.

Prof. Whittaker says with MERS, “the primary infection is in the lungs, and even there it infects additional cell types.” These additional cell types include immune cells, which may offer the virus a way to spread to the rest of the body, he adds.

The researchers also found furin activates the cleavage sites at different stages of the virus life cycle. One point is when the virus is assembled inside a host cell, another is when the virus makes it way out of the cell to the surface, and a third is when the virus finds a new cell and fuses with its membrane.

They suggest one avenue for treatment could be to block furin at a specific point in the host cell entry process.

Viruses mutate all the time, posing challenges for treatment developers. One way they mutate is to change the protease they use for activation. This study highlights an example of how flexible coronaviruses are in the way they alter their cleavage mechanism: “They are extremely adaptable,” says Dr. Millet.

Prof. Whittaker and Dr. Millet suspect the MERS-CoV strain that infects humans mutated about 2.5 years ago from a strain in camels. This was first suggested in 2013, when a Lancet study gave the first hint that camels could be a reservoir for MERS.

Camels are an important feature of everyday life in many cultures in North Africa and the Middle East, providing many opportunities for people to become exposed to camel secretions such as milk and urine, which can be possible routes to human infection, Prof. Whittaker explains.

At present human-to-human spread is relatively rare in MERS, except during hospital-acquired-outbreaks, note the researchers.

The MERS outbreak in Saudi Arabia began in April and was largely confined to hospitals. Cases have fallen, and it appears that the outbreak has been contained.

Following a recent meeting of its International Health Regulations (IHR) Emergency Committee to discuss the outbreak, a WHO statement notes that “although transmission in health care settings is still occurring in small clusters, transmission seems generally contained,” and that current data suggests transmission could be seasonal, “with an upsurge expected next spring.”

In earlier statements the WHO have emphasized the importance of infection prevention and control measures in containing the spread of MERS, and note it is not possible to identify infected patients early because the early symptoms are non-specific.

Poor infection prevention and control, lack of professional expertise and equipment have been cited as reasons for the rapid spread of Ebola in the epidemic currently raging in West Africa and threatening to spread to other continents.