MERS virus cell entry mechanism is possible drug target

Date: Oct-15-2014 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.

Furin protease activates the fusion of MERS with host cell membranes

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.

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.

Treatment option may lie in blocking MERS furin at cell entry stage

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.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.