Scientists at Brookhaven National Laboratory are working at a feverish pace to determine which drug molecules can block the virus that causes COVID-19 from attaching to human cells and replicating inside them.
Researchers from the world-renowned Long Island lab also are using computers to cull scores of scientific papers and pinpoint findings for scientists around the globe.
“I am 100% sure science will solve this problem,” said John Hill, director of Brookhaven Lab’s National Synchrotron Light Source II and chair of the lab’s COVID-19 working group. “And we could well be part of that solution — either something that directly comes out of Brookhaven or something that somebody works on because they heard about what we did.”
There are more than 2.2 million confirmed cases of COVID-19 globally, according to the World Health Organization, including over 152,000 deaths. On Long Island, the number of positive cases has topped 56,000 with more than 2,000 deaths, according to the state Health Department.
Brookhaven is one of 10 labs across the country overseen and primarily funded by the U.S. Department of Energy’s Office of Science. The facility is used by scientists and academic researchers conducting publicly accessible work, and it's where pharmaceutical and other companies can conduct proprietary research.
The lab is operated through a partnership between Stony Brook University and Battelle, a nonprofit science and technology development firm.
Hill said roughly 90% of the lab’s 2,500-plus employees are working from home. There is a small crew on hand at Brookhaven to run the synchrotron, a large accelerator about a kilometer in circumference that generates intense beams of X-ray, ultraviolet and infrared light to capture atomic-level images of materials, including molecules.
Before COVID-19, the synchrotron and its 30 beam lines could be used for a diverse array of experiments involving, for example, toxins in a plant leaf, how cellphone batteries die or even particles of dust brought in from outer space, Hill said. It also helps scientists study the structure of proteins.
“What they are doing now is trying to understand the structure of proteins that are relevant to COVID-19,” he said.
Microscopic images of SARS-CoV-2, the novel coronavirus that causes the disease COVID-19, show particles with crown-like protein spikes.
Those spike proteins bind with human cells, essentially opening them up and dumping in the contents of the virus, Hill said.
“Then it takes over the human cell and starts producing new virus particles,” he explained.
Researchers hope to find molecules that will stop the virus from binding with human cells.
“If you put another molecule in between those two … it can stop the whole thing from happening, or at least slow it down,” he said. “What we need to understand is which proteins from the virus are binding with which proteins in the human cell.”
Scientists are growing proteins from the virus, adding molecules of existing drugs and creating a crystal. By utilizing equipment jointly funded by the DOE and National Institutes of Health, they can view that crystal to see if the drug has an impact on virus replication.
“When we look at them with X-rays, we can get the structure very clearly,” Hill said.
But the number of potential compounds that could be used to possibly block the virus from infecting cells is mind-boggling — about 1.2 billion, according to Kerstin Kleese van Dam, director of the Computational Science Initiative at Brookhaven National Lab.
That’s one of the situations where computing research efforts can help.
Using a method called docking, scientists can calculate whether a drug molecule fits a druggable pocket — an opening in the protein structure — and how well it is likely to bind there, van Dam said.
Drug candidates that bind strongly are more likely to disrupt the protein function and stop the virus from causing infection, she said. Large libraries of molecules can be screened for good candidates.
“We are working together with other national labs,” she said. “We are splitting up the work to get through this as quickly as possible.”
Computational scientists at Brookhaven who usually work in other disciplines, such as physics or nanoscience, have stepped up, van Dam said.
Another challenge is wading through the mountains of scientific literature — about 40,000 publications — that have been published since the start of the COVID-19 pandemic, along with even more from previous coronavirus outbreaks such as SARS and MERS.
“The volume of information being published makes it hard for scientists to read all the material and work out what exactly is currently known,” van Dam said.
Brookhaven scientists are creating search mechanisms based on natural language processing to have computers help researchers navigate the publications.
“We really try to hone it down,” van Dam said. “You can search for very specific terms through the text. With a normal search engine, you type in a few words you are interested in and you get everything under the sun.”