The molecule, a modified peptide, was extracted from the relatively huge protein shell of a common virus that is a frequent cause of childhood diarrhea, according to the research conducted by a team at Eastern Virginia Medical School and Children's Hospital of The King's Daughters.
The discovery marks a quantum leap toward clinical application by creating a powerful effect with a molecule small enough to be used in medications.
"This puts us in a position to move rapidly from in-vitro testing to in-vivo testing," says Neel Krishna, PhD, an assistant professor of microbiology and molecular cell biology at EVMS and a pediatric virologist at CHKD.
The publication comes almost five years after Dr. Krishna and Kenji Cunnion, MD, an associate professor of pediatrics at EVMS and an infectious disease specialist with Children's Specialty Group at CHKD, inserted a shell of a virus that causes childhood diarrhea into a Petri dish primed to measure the response of a primordial component of the human immune response known as the complement system.
The complement reaction completely stopped.
"Being able to pharmacologically modulate the complement system could have a huge impact on the practice of medicine, potentially saving the lives of victims of hemorrhagic shock, heart attack patients, and even infants who have suffered prolonged hypoxia," says Dr. Krishna. "It could also have a significant impact on treating a wide range of autoimmune and inflammatory diseases."
The complement system is one of the oldest surviving remnants of the earliest life forms and exists in almost identical from in everything from seagulls to starfish.
It developed during millions of years in which the deadliest threat to all life forms, including humans, was not car accidents, heart attacks or the rejection of transplanted organs but infectious disease.
A complex cascade of dozens of biochemical reactions is designed to launch an attack that destroys the membranes of cells damaged by infection.
After trauma has left cells without oxygen for too long, the complement system kicks in when oxygen returns and lays waste to damaged cells that might otherwise survive. This is known as a reperfusion injury, and in some case occurs over a series of days.
In heart attacks, the death of heart cells during reperfusion can be irreversible and lethal. Multiple organ dysfunction syndrome caused by reperfusion injury is the leading cause of death in surgical patients and in trauma patients who survive the first 24 hours.
The inflammatory response also plays a major role in autoimmune and inflammatory diseases such as rheumatoid arthritis.
In earlier published research, the authors showed that the introduction of the harmless protein shell that encases the astrovirus, which causes pediatric diarrhea, shuts down two of the three methods used by the complement system to destroy damaged cells, but doesn't interfere with the part of complement reaction that can offer protection from invading pathogens.
The molecule that modulated the complement cascade, however, was relatively large, consisting of 787 amino acids, too sizable to be used therapeutically.
By meticulously testing smaller shards of the shell, researchers found and then modified a shard consisting of just 30 amino acids that actually was more effective than the larger molecule. That smaller segment, a modified peptide dubbed E23A, makes it a viable candidate for in-vitro testing of the compound.
"In-vitro testing is a significant step toward developing a drug that can be used therapeutically," says Dr. Krishna.
Doug Gardner | EurekAlert!
Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel
Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
21.09.2017 | Physics and Astronomy
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine