"By unlocking the three-dimensional structure of this enzyme -- known as papain-like-protease (PLpro) -- we now have a molecular road map to design new drugs that could potentially treat SARS-infected patients, or perhaps patients suffering from other SARS-related illnesses such as the common cold, bronchitis or pneumonia," said Andrew Mesecar, associate professor of pharmaceutical biotechnology in the UIC College of Pharmacy. "We are attempting to use the same approach that has been accomplished in designing effective drugs against HIV protease, which has led to the development of new drugs to fight the AIDS virus."
The research is published in the March 27 issue of the Proceedings of the National Academy of Sciences.
Mesecar said that the knowledge gained from this new atomic structure -- the first-ever reported on this class of proteases -- has the potential to go beyond the treatment of patients infected with the coronavirus that causes SARS.
Coronaviruses, which produce upper respiratory tract infections, were discovered in the late 1960s. The viruses are responsible for 10 percent to 30 percent of all common colds. Recently, two new coronaviruses -- NL63 and HKU1 -- were found to cause many cases of severe pneumonia in children and the elderly throughout the world, he said.
"NL63 and HKU1 infections are severe and often lead to hospitalization," Mesecar said. "It is believed these viruses have been around a long time, but only recently have we developed the technology to identify and detect them. The SARS outbreak and quick response of the scientific community has led to the rapid development of such technology."
SARS was first reported in Asia in early 2003. Over the next several months the illness spread to more than 29 countries in North and South America, Europe and Asia before it was contained. It begins with a high fever, headache and body aches. About 10 percent to 20 percent of patients have diarrhea, and after two to seven days, a dry cough may develop. Most patients develop pneumonia. The infection spreads by close personal contact, often through coughing or sneezing.
According to the World Health Organization, 8,098 people worldwide were diagnosed with SARS during the 2003 outbreak; 774 died. There were 29 cases reported in the United States, with no fatalities.
The papain-like-protease enzyme is essential for viral replication and infection of all of the coronaviruses involved in upper respiratory infections. Eliminating the enzyme should stop the infection, Mesecar said.
During the UIC study, graduate student Kiira Ratia, a member of Mesecar’s research team, used X-ray crystallography, a technique that involves bombarding a crystalline form of the enzyme with an intense beam of X-rays that are bent by atoms in the molecules to unlock the details of the molecular structure. The X-ray studies were conducted at Argonne National Laboratory’s Advanced Photon Source.
As the X-rays leave the crystal, a unique pattern is created on an ultra-high resolution charge-coupled device camera, a sensor for recording images often used in digital photography and astronomy. The images were then interpreted by computer to reconstruct the positions of all the component atoms.
"We have already discovered compounds that can bind to these pockets and inhibit the activity of this enzyme," Mesecar said. "We have made remarkable progress in a short period of time in generating lead drug-like compounds against the enzyme."
Sam Hostettler | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy