11 Jun 2014, BioSpectrum Bureau , BioSpectrum
Singapore: A Purdue University team headed by Mr Andrew Mesecar has made a breakthrough by unraveling the mystery around how to disable a part of the SARS virus, responsible for hiding it from the immune system.
Mr Mesecar explained in a report, "This is the first step toward creating a weakened and safe virus for use in an attenuated live vaccine. This also could serve as a molecular roadmap for performing similar studies on other coronaviruses, like MERS, because this enzyme appears to be common to all viruses within this family." There is currently no treatment or vaccine for the virus, which has an estimated fatality rate of 30 percent, according to the Centers for Disease Control and Prevention.
Scientists captured the molecular structure of a key SARS enzyme, papain-like protease and revealed how it strips a host cell of the proteins ubiquitin and ISG15, which is involved in triggering an immune response.
"With most viruses, when a cell is infected it sends out an alarm triggering an immune response that fights the infection, but successful viruses are able to trick the immune system," he said. "By clipping off these two proteins, SARS short circuits the host cell's signaling pathways and prevents it from alerting the immune system to its presence. By removing these proteins, the enzyme serves as a biological cloaking system for the SARS virus that allows it to live and replicate undetected."
"The disruption in its natural signaling pathways also causes an infected cell to miscommunicate with the cells around it which leads to a response that eventually kills those cells," he said.
The deadly virus has caused around 774 deaths. The virus can be transmitted through coughing or sneezing and the infection can quickly spread from person to person. SARS spread through two dozen countries over a period of a few months before it was contained.
In addition to hiding the virus from the immune system, the SARS papain-like protease, or PLpro, enzyme also is responsible for snipping the viral polyprotein into individual proteins that are essential for viral replication. While some treatments are designed to prevent viral replication, researchers working on a vaccine must retain this function, he said.
"The goal in engineering a SARS virus that could be used as a vaccine is to create one that replicates in cells but is unable to fend off the body's immune response," he added. "We want enough viral particles to be generated to properly prime the immune system to fight off a true infection, but without the virus being able to cause illness in the vaccinated individual."