Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.
Under the electronic microscope, the Ebola particles looked like tiny round bubbles floating inside human cells. Except these Ebola particles couldn't get free from their confinement.
They were trapped inside their bubbles, unable to release their RNA into the human cells to start replicating. These cells stopped the Ebola infection. And they did it on their own, without any medications, albeit in a petri dish of immunologist Adam Lacy-Hulbert. He studies how cells fight infections at the Benaroya Research Institute in Seattle, Washington.
These weren't just any ordinary human cells. They had a specific gene turned on—namely CD74, which typically wouldn't be on. Lacy-Hulbert's team was experimenting with turning various genes on and off to see what made cells fight viral infections better. One particular form of the CD74 gene did the trick. Normally, the Ebola particles would use the cells' own proteases—enzymes that are often called "molecular scissors" because they slice proteins—to cut the bubbles open. But CD74 produced a protein that blocked the scissors from cutting the bubbles, leaving Ebola trapped.
A New Frontier in the Making<p>The idea of making human cells genetically resistant to infections—and possibly other stressors like cancer or aging—has been considered before. It is the concept behind the Genome Project-write or <a href="https://engineeringbiologycenter.org/" target="_blank" rel="noopener noreferrer"><u>GP-write project</u></a>, which aims to create "ultra-safe" versions of human cells that resist a variety of pathogens by way of "recoding" or rewriting the cells' genes.<br></p><p>To build proteins, cells use combinations of three DNA bases called codons to represent amino acids—the proteins' building blocks. But biologists find that many of the codons are redundant so if they were removed from all genes, the human cells would still make all their proteins. However, the viruses, whose genes would still include these eliminated redundant codons, would no longer successfully be able to replicate inside human cells. </p><p>In 2016, the GP-Write team successfully reduced the number of <a href="https://science.sciencemag.org/content/353/6301/819.full" target="_blank" rel="noopener noreferrer"><u><em>Escherichia coli's</em> codons from 64 to 57</u></a>. Recoding genes in all human cells would be harder, but some recoded cells may be transplanted into the body, says Harvard Medical School geneticist George Church, the GP-Write core founding member. </p><p>"You can recode a subset of the body, such as all of your blood," he says. "You can also grow an organ inside a recoded pig and transplant it." </p><p>Church adds that these methods are still in stages that are too early to help us with this pandemic.</p>
LeapsMag exclusively interviewed Church in 2019 about his latest progress with DNA recoding:<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="957f3bcdeaed354f15a886bb184bbd62"><iframe lazy-loadable="true" src="https://www.youtube.com/embed/IjjSg8ED0Jw?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
The Push for Clinical Trials<p>In the meantime, interferons may prove an easier medicine. Lacy-Hulbert thinks that interferon gamma might play a role in activating the CD74 gene, which gums up the molecular scissors. There also may be other ways to activate that gene. "So we are now thinking, can we develop a drug that mimics that actual activity?" he says.<br></p><p>Some interferons are already manufactured and used for treating certain diseases, including multiple sclerosis. Theoretically, nothing prevents doctors from prescribing interferons to Covid patients, but it must be done in the early stages of infection—to stimulate genes that trigger cellular defenses before the virus invades too many cells and before the immune systems mobilizes its big guns.</p><p>"If my father who is 70 years old tests positive, I would recommend he takes interferon as early as possible," says Zhang. But to make it a mainstream practice, doctors need clear prescription guidelines. "What would really help doctors make these decisions is clinical trials," says Casanova, so that such guidelines can be established. "We are now starting to push for clinical trials," he adds.</p>
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
When COVID-19 cases were surging in New York City in early spring, Chitra Mohan, a postdoctoral fellow at Weill Cornell, was overwhelmed with worry. But the pandemic was only part of her anxieties. Having come to the United States from India on a student visa that allowed her to work for a year after completing her degree, she had applied for a two-year extension, typically granted for those in STEM fields. But due to a clerical error—Mohan used an electronic signatureinstead of a handwritten one— her application was denied and she could no longerwork in the United States.
"I was put on unpaid leave and I lost my apartment and my health insurance—and that was in the middle of COVID!" she says.
Meanwhile her skills were very much needed in those unprecedented times. A molecular biologist studying how DNA can repair itself, Mohan was trained in reverse transcription polymerase chain reaction or RT-PCR—a lab technique that detects pathogens and is used to diagnose COVID-19. Mohan wanted to volunteer at testing centers, but because she couldn't legally work in the U.S., she wasn't allowed to help either. She moved to her cousin's house, hired a lawyer, and tried to restore her work status.
Neel in his lab with postdocs
(Courtesy of Neel)
Dogan on Zoom talking to his fellow union members of the Academic Researchers United, a union of almost 5,000 Academic Researchers.
(Credit: Ceyda Durmaz Dogan)