Nav: Home

Scientists enlist engineered protein to battle the MERS virus

May 19, 2017

In June 2012, a 60 year-old man with flu-like symptoms walked into a private hospital in Jeddah, Saudi Arabia. Two weeks later, he died from multiple organ failure, becoming the first victim of a mysterious virus that came to be known as Middle East Respiratory Syndrome or MERS.

The World Health Organization (WHO) has identified MERS as an urgent threat with no vaccine or treatment in sight. This could change thanks to a new anti-viral tool, developed by University of Toronto researchers.

Writing in the journal PLoS Pathogens, the team led by Professor Sachdev Sidhu, of the Donnelly Centre for Cellular and Biomolecular Research and Department of Molecular Genetics, describe how they turned ubiquitin, a staple protein in every cell, into a drug capable of thwarting MERS in cultured human cells. Because the technology can be applied to a wide range of pathogens, it could become a game-changer in anti-viral therapeutics with implications for human health and the farming industry.

"Vaccines are important for prevention, but there is a great need for anti-viral medicines to treat people who have become infected," says Dr. Wei Zhang, a postdoctoral research fellow in Sidhu's lab who did most of the work on the study.

MERS is similar to SARS, the virus that killed almost 800 people in a 2002 global epidemic. Both kill upwards of a third of people infected and, like many viruses, emerged from animals--bats and camels in the case of MERS--after mutating into a form capable of infecting human cells. Although MERS has so far been detected in 27 countries since the first case emerged in 2012, the outbreak has largely been contained within Saudi Arabia, according to the WHO.

Like many viruses, MERS works by hijacking the ubiquitin system in human cells composed of hundreds of proteins that rely on ubiquitin to keep the cells alive and well. Upon infection, viral enzymes alter ubiquitin pathways in a way that allows the virus to evade the immune defense while multiplying and destroying the host tissue as it spreads in the body.

"Viruses have evolved proteins that allow them to hijack host proteins. We can now devise strategies to prevent this from happening," says Zhang.

Zhang and colleagues engineered the human ubiquitin protein into a new form that paralyses a key MERS enzyme, stopping the virus from replicating. These synthetic ubiquitin variants act quickly, completely eliminating MERS from cells in a dish within 24 hours.

The researchers also created UbVs that blocks the Crimean-Congo virus, the cause of a haemorrhagic fever that kills about 40 per cent of those infected.

And they're designed to only target only the virus -- hopefully minimizing side effects in any future drug.

But before these engineered proteins can be developed into medicine, researchers first must find a way to deliver them into the right part of the body. For this, Zhang and Sidhu are working with Dr. Roman Melnyk, a biochemist in The Hospital for Sick Children and a world expert in protein delivery.

The team is also investigating the possibility of finding drugs that work in a similar manner but can already cross the cell membrane.

It is likely that the proteins will be tested first in plants and animals where regulatory approvals are less strict than they are for human drugs. "We are also working on an engineered ubiquitin that targets a corn virus responsible for destroying large swaths of corn fields in North America, with colleagues in Manitoba," says Zhang.

In the meantime, Zhang will continue to improve delivery of his designer proteins to human cells that target not only MERS but also other viruses. He hopes others will follow suit.

"With our tool, we can quickly generate anti-viral medicine and we hope that our method will inspire other researchers to try it out against diverse pathogens," says Zhang.
-end-
The study was done in collaboration with Professor Marjolein Kikkert, of Leiden University Medical Centre in The Netherlands and Professor Brian Mark at the University of Manitoba.

University of Toronto

Related Proteins Articles:

Discovering, counting, cataloguing proteins
Scientists describe a well-defined mitochondrial proteome in baker's yeast.
Interrogating proteins
Scientists from the University of Bristol have designed a new protein structure, and are using it to understand how protein structures are stabilized.
Ancient proteins studied in detail
How did protein interactions arise and how have they developed?
What can we learn from dinosaur proteins?
Researchers recently confirmed it is possible to extract proteins from 80-million-year-old dinosaur bones.
Relocation of proteins with a new nanobody tool
Researchers at the Biozentrum of the University of Basel have developed a new method by which proteins can be transported to a new location in a cell.
Proteins that can take the heat
Ancient proteins may offer clues on how to engineer proteins that can withstand the high temperatures required in industrial applications, according to new research published in the Proceedings of the National Academy of Sciences.
Designer proteins fold DNA
Florian Praetorius and Professor Hendrik Dietz of the Technical University of Munich have developed a new method that can be used to construct custom hybrid structures using DNA and proteins.
The proteins that domesticated our genomes
EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human genome.
Rare proteins collapse earlier
Some organisms are able to survive in hot springs, while others can only live at mild temperatures because their proteins aren't able to withstand such extreme heat.
How proteins reshape cell membranes
Small 'bubbles' frequently form on membranes of cells and are taken up into their interior.

Related Proteins Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...