Scientists design proteins that could keep coronavirus from spreading COVID-19




 

Imagine being able to ward off COVID-19 just by spritzing a nasal spray into your nostrils. It may not be just your imagination: Researchers at the University of Washington have designed a batch of synthetic proteins that could conceivably block the coronavirus behind this year's pandemic from gaining a foothold.

"Although extensive clinical testing is still needed, we believe the best of these computer-generated antivirals are quite promising," Longxing Cao, a postdoctoral scholar at UW's Institute for Protein Design, said in a news release.

Cao is the lead author of a study about the protein-building experiment, published today by the journal Science. It's the latest innovation to come from the emerging field of protein engineering, and the technique could revolutionize how drugs are developed to counter future pandemics.

It may not be too late to counter COVID-19 as well. "We are working to get improved versions … deployed to fight the current pandemic," senior study author David Baker, the director of the Institute for Protein Design, told GeekWire in an email.

The technique involves creating small-molecule proteins, or mini-binders, that are custom-designed to latch onto the spiky molecular structures that are scattered around the surface of SARS-CoV-2, the virus that causes COVID-19.

The spikes on the virus do their dirty work by fitting into molecular-scale receptors on the surfaces of cells, much like fitting a key into a lock to gain entry to someone's house. Once the virus "unlocks" a receptor, it gains entry to the cell, hijacks its chemical machinery and churns out more virus particles to spread the infection.

Baker, Cao and their colleagues used high-powered computers to design more than 2 million candidate proteins that could conceivably gum up the works for the virus' spike protein. More than 118,000 of the most promising candidates were synthesized and tested on lab-grown cells.

Agilent Technologies and Twist Bioscience manufactured the synthetic proteins for testing, and researchers at the Washington University School of Medicine in St. Louis used cryo-electron microscopy to document how the mini-binders interacted with the spike proteins. A distributed-computing network called Rosetta@home helped screen the candidates.

The best candidate, known as LCB1, blocked the effectiveness of the spike protein with six times the potency of monoclonal antibodies, which offer an alternate route for preventing infection. What's more, Cao said the mini-binders are "much easier to produce and far more stable, potentially eliminating the need for refrigeration."

The researchers say their mini-binders seem well-suited for a powdery aerosol or spray that could be delivered into the respiratory system through the nose. "There is not much precedent in protein antivirals that would be delivered directly into the respiratory system - this is the sweet spot for our designs, we believe," Baker said.

Now LCB1 is being evaluated in rodents, and Baker said there's interest in taking a candidate COVID-19 antiviral drug into human clinical trials. "We're currently exploring that," he said, without providing further details.

Once the technique is perfected and automated, protein antivirals could be designed and produced for testing with the first month of a viral outbreak, Baker said. The technique also could be adapted to create new types of diagnostics for viral infections.

In addition to Cao and Baker, authors of the paper published by Science, "De Novo Design of Picomolar SARS-CoV-2 Miniprotein Inhibitors," include Inna Goreshnik, Brian Coventry, James Brett Case, Lauren Miller, Lisa Kozodoy, Rita Chen, Lauren Carter, Lexi Walls, Young-Jun Park, Lance Stewart, Michael Diamond and David Veesler.

The work was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, The Audacious Project at IPD, Eric and Wendy Schmidt by recommendation of the Schmidt Futures program, the Open Philanthropy Project, an Azure computing resource gift for COVID-19 research provided by Microsoft, and the Burroughs Wellcome Fund.

COMMENTS

More Related News

Houston study: More contagious coronavirus strain now dominates
Houston study: More contagious coronavirus strain now dominates
  • US
  • 2020-09-23 22:22:16Z

The Houston researchers said patients infected with the variant strain had significantly higher amounts of the virus on initial diagnosis. Previous studies have shown that the coronavirus is mutating and evolving as it adapts to its human hosts.

Possible virus vulnerability discovered; about 20% of people with COVID-19 remain asymptomatic
Possible virus vulnerability discovered; about 20% of people with COVID-19 remain asymptomatic
  • US
  • 2020-09-23 19:30:25Z

The spike protein on the novel coronavirus that helps it break into healthy cells has a tiny "pocket" that could make it vulnerable to antiviral drugs, researchers have discovered. In a paper published on Monday in Science, researchers note that common-cold-causing rhinoviruses have a similar pocket, and drugs that fit into the pocket by mimicking fatty acids like LA have lessened symptoms in human clinical trials. This suggests, they say, that drugs developed to target the pocket on the coronavirus spike protein might help eliminate COVID-19.

Coronavirus updates: J&J begins late-stage trial for single-shot vaccine; Ginsburg public viewing to be held outside Supreme Court
Coronavirus updates: J&J begins late-stage trial for single-shot vaccine; Ginsburg public viewing to be held outside Supreme Court

Miami-Dade County schools will return to in-person instruction beginning Oct. 14. Donald Trump says U.S. death toll is "a shame." Latest COVID news.

What you need to know about the coronavirus right now
What you need to know about the coronavirus right now
  • US
  • 2020-09-23 09:20:58Z

Wisconsin Governor Tony Evers on Tuesday declared a new public health emergency and extended a face mask mandate into November to fight a coronavirus flareup in his state, as the number of people who have died across the United States since the pandemic began passed 200,000. In-person social gatherings have led to cases in Wisconsin skyrocketing among people aged 18 to 24, Evers said and pleaded with students who returned to colleges for the fall semester to stay out of bars and wear masks. COVID-19 infections have surged in Canada and if people do not take stringent precautions, they could balloon to exceed levels seen during the first wave of the pandemic, health officials warned on...

Colleges reopenings in-person likely added 3,000 U.S. COVID-19 cases per day: study
Colleges reopenings in-person likely added 3,000 U.S. COVID-19 cases per day: study
  • US
  • 2020-09-22 20:13:11Z

The findings call into question the practicality of face-to-face classes during the COVID-19 pandemic, and are important as colleges and universities plan their spring 2020 semesters, said researchers from the University of North Carolina at Greensboro, Indiana University, the University of Washington and Davidson College. To track COVID-19 cases and study their association with students attending classes at college campuses, the team used location data from a database of cellphone users who agreed to share information. The researchers noted significant increases in counties where colleges had reopened for face-to-face instruction, especially in and around campuses with students who...

Leave a Comment

Your email address will not be published. Required fields are marked with *

Cancel reply

Comments

Top News: Economy