Better treatment for MERS in offing

Researchers, including those of Indian-origin, have found molecules that shut down the activity of an essential enzyme in the deadly MERS virus, paving the way for better treatments for those infected.
"The virus affects people differently and for many the symptoms are not life-threatening, but for others it can lead to severe respiratory distress," said Andrew Mesecar, Professor at the Purdue University, who led the research.
Mesecar and Arun Ghosh, Professor of Chemistry and Medicinal Chemistry and Molecular Pharmacology at Purdue and colleagues identified molecules that inhibit an enzyme essential to the Middle East Respiratory Syndrome, or MERS, virus replication.

They also discovered a characteristic of the enzyme that is very different from other coronaviruses, the family of viruses to which MERS-CoV belongs.
"This enzyme is a prime target - an Achilles' heel of the virus - and we were excited to find an inhibitor that worked, but we were puzzled by the results," Mesecar said.
The team, including graduate student Sakshi Tomar, targeted an enzyme within the MERS virus called 3C-like protease, without which the virus cannot create more viruses to further an infection.

Once inside the cell, the virus creates a long strand of a large viral protein that must be cut at specific points to release individual proteins that serve various functions in building new virus particles.

The 3C-like protease is responsible for making 11 of the necessary cuts for successful viral replication and without it the process shuts down, Mesecar said.
A single copy of the 3C-like protease must find and bond to another identical 3C-like protease "twin" in order to perform its function.
Proteins that require bonding to a twin protein to perform their function are called dimers.
The team found that the MERS protease is unusual in that it does not have a strong attraction to its identical proteases and therefore does not readily form its dimer.
This means an individual MERS 3C-like protease will remain single much longer and its dimer will break apart much more easily than the SARS protease or those of other coronaviruses, Mesecar said.

By sending another molecule to attach to and block this key site, the protease would be unable to bind to the strand of viral protein and viral replication would be shut down.
As the team increased the dose of the inhibitor, the scientists found that it would fill the target sites of all of the 3C-like proteases and its activity would be successfully blocked, he said.
"The MERS virus is in the international spotlight as South Korea faces the largest MERS outbreak outside the Middle East," researchers said.
"The World Health Organisation (WHO) reported 19 deaths and 154 confirmed cases in its most recent update," they said.

The research was published in the Journal of Biological Chemistry.