t typically takes many years of experiments to develop a new medicine. Although vaccines to protect against disease from the novel coronavirus are starting to reach clinics around the world, patients and doctors will still need treatments to manage COVID-19 symptoms for some time.
At Pacific Northwest National Laboratory (PNNL), computational biologists, structural biologists, and analytical chemists are using their expertise to safely accelerate the design step of the COVID-19 drug discovery process.
Rather than finding a new drug by trial and error, scientists are taking the three-dimensional structures of proteins from the novel coronavirus and using computer modeling and machine learning to identify a unique molecule that best fits inside a binding pocket on a protein’s surface. Ideally, that molecule clogs the viral protein and prevents it from functioning.
“Drug research and development is a complex, costly, and time-consuming process, particularly considering the majority of molecules advanced from the design phase fail in clinical trials,” said PNNL computational data scientist Neeraj Kumar. “Computer-based screening incorporates chemical information during the design process to increase a drug candidate’s potential for success in clinical testing.”
Developing an approach to speed drug discovery during this pandemic could also reveal new design steps that might be useful during the next outbreak.
Clogging coronavirus proteins
There are almost 30 different proteins in this novel coronavirus that are potential targets for COVID-19 drug discovery. Combine that with millions of molecules that are potential drug candidates, and the possibilities for matching molecules to specific proteins are mind-boggling.
To narrow the options towards molecules with potential to become medicines, Kumar and his team first use molecular docking to virtually screen libraries of known molecules and regulatory-approved drugs. Ones that fit in the binding pocket of a particular coronavirus protein make the short list for the next step of the process: testing the fit with actual proteins and molecules.
Experimental scientists then combine the molecules on this short list with purified coronavirus protein and “weigh them” with native mass spectrometry to see if the protein picked up the molecule. This technique measures interactions between the protein and the molecules and can confirm the predicted binding.
Image Credit: Timothy Holland | Pacific Northwest National Laboratory
Post by Amanda Scott, NA CEO. Follow her on twitter @tantriclens
Thanks to Heinz V. Hoenen. Follow him on twitter: @HeinzVHoenen
News
Nasal Vaccines: Stopping the COVID-19 Virus Before It Reaches the Lungs
The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve [...]
NASA Tracking a Huge, Growing Anomaly in Earth’s Magnetic Field – with video
NASA is actively monitoring a strange anomaly in Earth's magnetic field: a giant region of lower magnetic intensity in the skies above the planet, stretching out between South America and southwest Africa. This vast, developing [...]
New, Better Models Show How Infectious Diseases Like COVID-19 Spread
Infectious diseases such as COVID-19 can spread rapidly across the globe. Models that can predict how such diseases spread will strengthen national surveillance systems and improve public health decision-making. The COVID-19 pandemic has emphasized the [...]
Human Antibodies Discovered That Can Block Multiple Coronaviruses Including COVID-19
Results from a Scripps Research and UNC team pave the way for a vaccine and therapeutic antibodies that could be stockpiled to fight future coronavirus pandemics. A team of scientists from Scripps Research and [...]
Nanotechnology could be used to treat lymphedema
The human body is made up of thousands of tiny lymphatic vessels that ferry white blood cells and proteins around the body, like a superhighway of the immune system. It's remarkably efficient, but if [...]
DNA Nanotechnology Tools – From Design to Applications
Suite of DNA nanotechnology devices engineered to overcome specific bottlenecks in the development of new therapies, diagnostics, and understanding of molecular structures. DNA nanostructures with their potential for cell and tissue permeability, biocompatibility, and [...]
Regenerating bone with deer antler stem cells
Scientists from a collection of Chinese research institutions collaborated on a study of organ regeneration in mammals, finding deer antler blastema progenitor cells are a possible source of conserved regeneration cells in higher vertebrates. [...]
AI Takes On Cancer: Analysis of Mutations Could Lead to Improved Therapy
Cancer is a complex and diverse disease, and its range of associated mutations is vast. The combination of these genomic changes in an individual is referred to as their “mutational landscape.” These landscapes vary [...]
Exposing tumours to bacteria converts immune cells to cancer killers
New research on inflammation could lead to better treatments to improve outcomes for people with advanced or previously untreatable cancers. Introducing bacteria to a tumour’s microenvironment creates a state of acute inflammation that triggers [...]
Smart nanotechnology for more accurate delivery of insulin
More efficient and longer lasting glucose-responsive insulin that eliminates the need for people with type 1 diabetes to measure their glucose levels could be a step closer thanks to a Monash University-led project. Published [...]
Efficiently Harvesting Rare Earth Elements From Wastewater Using Exotic Bacteria
The novel strains of cyanobacteria exhibit a fast and efficient “biosorption” of rare earth elements, making recycling possible. Rare earth elements (REEs) are a set of 17 metallic elements that possess similar chemical properties. [...]
Resisting Treatment: Cancer Cells Shrink or Super-Size To Survive
A new approach to image analysis has uncovered how cancer cells manipulate their size as a means of resisting treatment. Researchers have discovered that cancer cells are capable of either shrinking or super-size themselves [...]
New Research Explains Why Children Avoid Severe COVID-19 Symptoms
According to new research, children exhibit a robust initial immune response to the coronavirus, however, they are unable to transfer this response to long-lasting memory T cells like adults do. Researchers led by scientists [...]
Scientists Unravel Protein Map of Mitochondria
A new study sheds light on the organization of proteins within mitochondria. Mitochondria, the “powerhouses” of cells, play a crucial role in the energy production of organisms and are involved in various metabolic and [...]
Mystifying Trapping Phenomenon: A Surprising Way To Catch a Microparticle
New insights could advance microfluidics and drug delivery systems. New study finds obstacles can trap rolling microparticles in fluid Through simulations and experiments, physicists attribute the trapping effect to stagnant pockets of fluid, created [...]
New Alzheimer’s Treatment: Blocking T Cells To Prevent Neurodegeneration
Findings, in mice, open up drug development possibilities for brain diseases linked to tau protein. Nearly two dozen experimental therapies targeting the immune system are in clinical trials for Alzheimer’s disease, a reflection of the growing [...]
