Jonathan Dordick, Ph.D., and his lab mates at Rensselaer Polytechnic Institute (RPI) weren’t thinking about coronaviruses when they initially developed their “viral trap,” a DNA-based nanotechnology designed to capture and kill viruses floating in the bloodstream. But as the COVID-19 pandemic started to unfold, they realized they may be able to transform their invention into a potential solution to the relentless virus—and they got to work on a plan to do so.
“We have something that can be tailored specifically to the virus,” said Dordick, professor of chemical and biological engineering at RPI, in an interview with FierceBiotechResearch. “There has been very rapid research that has come out in the last couple of months about the proteins on the surface of the coronavirus. Once we know their approximate location on the surface, and what the receptor is [on cells] that the virus targets, it allows us to very quickly tailor this DNA nanostructure” to COVID-19, he said. Dordick’s team has developed a research proposal, which includes testing the viral trap technology in animal models of COVID-19, he added.
RPI is one of several institutions stepping up with ideas of how to take existing research and pivot it toward potential solutions to COVID-19. And these ideas are not just bubbling up in academia. Some biotech startups are taking existing antiviral discoveries—or even technologies they initially developed to address very different diseases, like cancer—and offering to deploy them toward defeating the coronavirus.
It may take several months or even years for these efforts to bear fruit, at which point this pandemic may have ended, but that’s no deterrent, many scientists say. “We will see new viruses being passed from animals to humans again,” predicted Christian Peters, M.D., Ph.D., CEO of Pinpoint Therapeutics, in an interview with FierceBiotechResearch. Pinpoint is one of the companies that’s putting plans in place to target COVID-19. “We must have an armamentarium of different drugs with different mechanisms so we’re ready for the future that’s to come,” Peters said.
RPI’s viral trap is adaptable to a range of viruses due to its design, Dordick explained. The technology entails folding pieces of DNA into a five-point star that mimics the latching locations on human cells that viruses must bind to in order to infect their hosts. In a Nature Chemistry paper published in November 2019, they described how they used the folded DNA to rapidly detect the dengue virus in blood.
The next step would be to use the same nanotechnology platform to kill the virus once it’s snared in the trap. “In detecting the virus, we’re also preventing it from binding to its receptor,” he said. “We showed that the DNA binds to the proteins on the surface of the dengue virus, preventing them from infecting the target cell. In that way, we can inhibit the infection process.” Dordick’s team has shown that a similar approach is effective in preclinical models of influenza A and Zika virus, as well.
As for startup Pinpoint Therapeutics, it was founded on the discovery that drugs designed to combat the malaria virus may also have promise in fighting cancer—and now its scientists are taking their antiviral know-how and applying it to COVID-19. Pinpoint is developing drugs that inhibit PPT1, a pathway targeted by a class of antimalarial drugs known as chloroquines.
If that sounds familiar, it’s because President Donald Trump created a bit of an uproar earlier this month when he latched onto reports about the potential use of chloroquine against COVID-19 and said the U.S. would make it available by prescription “almost immediately.” Questions have since emerged about the effectiveness of the drug against the virus due to disappointing clinical trial results in China, but the FDA did issue emergency use authorization for the use of hydroxychloroquine in COVID-19 patients Monday.
Pinpoint’s approach revolves around a process called “autophagy,” in which cells recycle components so they can survive being attacked. Researchers at the University of Pennsylvania discovered that inhibiting PPT1 slows tumor growth—a finding that led to the formation of Pinpoint, which is now optimizing PPT1 inhibitors to test in cancer. Pinpoint has received seed funding from Kairos Ventures, which in February kicked in $1 million in debt funding to help accelerate the search for candidate drugs.
Peters said that the company’s scientific team realized inhibiting PPT1 would also interrupt the ability of COVID-19 to replicate. And because the drugs could have as much as 1,000-fold more potency than standard malaria treatments when it comes to inhibiting PPT1, the hypothesis is that they could be more effective against COVID-19 than hydroxychloroquine is.
Although it will take several months to complete the laboratory and animal studies needed to identify drug candidates against COVID-19, Peters believes the insights they gain will remain relevant, even if the pandemic has resolved by that time. “It’s important to look not just at the anti-viral components, but also at the anti-inflammatory properties that these drugs might have. The synergistic effects of less virus replication and less inflammation may actually be very beneficial in the treatment of coronaviruses.” And because there are so many viruses that are closely related to COVID-19, and there’s a risk that novel viruses will continue to emerge, Pinpoint’s scientists believe any new products that come from their research will find a place in the market, he said.
Some researchers who have devoted their careers to understanding coronaviruses are finding their expertise in high demand during this pandemic. One of them is Ralph Baric, Ph.D., professor of microbiology and immunology at the University of North Carolina (UNC) at Chapel Hill. Early discoveries in his lab led to Gilead Sciences' remdesivir, the investigational antiviral that’s now in clinical trials for COVID-19. Gilead, meanwhile, is making the drug available on a compassionate use basis for patients fighting COVID-19.
Now, another COVID-19 candidate has emerged from Baric’s lab. The drug, called EIDD-2801, is being developed by Ridgeback Biotherapeutics and Emory University’s nonprofit biotechnology company Drug Innovations at Emory (DRIVE).
UNC and Emory researchers described EIDD-2801 last week in a study that was preprinted on the Cold Spring Harbor Laboratory site bioRxiv. The researchers reported that the drug has “broad spectrum antiviral activity” against COVID-19 and several related viruses, including MERS-CoV. In mice infected with MERS-CoV or SARS-CoV, the drug decreased the viral load and improved lung function, they reported in the study (PDF).
EIDD-2801 is a ribonucleoside analog that’s designed to prevent RNA viruses from replicating. Ridgeback was already preparing for clinical trials of the drug in influenza when it and DRIVE’s scientists “immediately recognized that EIDD-2801 had the potential for treating COVID-19," George Painter, Ph.D., director of the Emory Institute for Drug Development and CEO of DRIVE, said in a statement.
The rapidly unfolding COVID-19 pandemic has inspired the scientific community to come up with solutions that will have the potential to save lives in the future, RPI’s Dordick said. “The key question after we get through this tragedy is, 'how will we avoid it again?'” Dordick said. “Will we have to shut everything down again, or can we have directed therapeutic development? I think we’re learning the lesson that we need rapid vaccine development and rapid therapeutic development. We’re going to learn an awful lot about what we can do.”