Designed Antiviral Proteins Inhibit SARS-CoV-2 in the Lab

Computer-designed small proteins have now been shown to protect lab-grown human cells from SARS-CoV-2, the coronavirus that causes COVID-19. The findings are reported today in Science.

In the experiments, the lead antiviral candidate, named LCB1, rivaled the best-known SARS-CoV-2 neutralizing antibodies in its protective actions. LCB1 is currently being evaluated in rodents.

Coronaviruses are studded with so-called Spike proteins. These latch onto human cells to enable the virus to break in and infect them. The development of drugs that interfere with this entry mechanism could lead to treatment of or even prevention of infection.

Institute for Protein Design researchers at the University of Washington School of Medicine used computers to originate new proteins that bind tightly to SARS-CoV-2 Spike protein and obstruct it from infecting cells.

Beginning in January, more than two million candidate Spike-binding proteins were designed on the computer. Over 118,000 were then produced and tested in the lab.

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

"They appear to block SARS-CoV-2 infection at least as well as monoclonal antibodies, but are much easier to produce and far more stable, potentially eliminating the need for refrigeration," he added.

The researchers created antiviral proteins through two approaches. First, a segment of the ACE2 receptor, which SARS-CoV-2 naturally binds to on the surface of human cells, was incorporated into a series of small protein scaffolds.

Second, completely synthetic proteins were designed from scratch. The latter method produced the most potent antivirals, including LCB1, which is roughly six times more potent on a per mass basis than the most effective monoclonal antibodies reported thus far.

Scientists from the University of Washington School of Medicine in Seattle and Washington University School of Medicine in St. Louis collaborated on this work.

"Our success in designing high-affinity antiviral proteins from scratch is further proof that computational protein design can be used to create promising drug candidates," said senior author and Howard Hughes Medical Institute Investigator David Baker, professor of biochemistry at the UW School of Medicine and head of the Institute for Protein Design. In 2019, Baker gave a TED talk on how protein design might be used to stop viruses.

To confirm that the new antiviral proteins attached to the coronavirus Spike protein as intended, the team collected snapshots of the two molecules interacting by using cryo-electron microscopy. These experiments were performed by researchers in the laboratories of David Veesler, assistant professor of biochemistry at the UW School of Medicine, and Michael S. Diamond, the Herbert S. Gasser Professor in the Division of Infectious Diseases at Washington University School of Medicine in St. Louis.

"The hyperstable minibinders provide promising starting points for new SARS-CoV-2 therapeutics," the antiviral research team wrote in their study pre-print, "and illustrate the power of computational protein design for rapidly generating potential therapeutic candidates against pandemic threats."

Longxing Cao, Inna Goreshnik, Brian Coventry, James Brett Case, Lauren Miller, Lisa Kozodoy, Rita E Chen, Lauren Carter, Alexandra C Walls, Young-Jun Park, Eva-Maria Strauch, Lance Stewart, Michael S Diamond, David Veesler, David Baker.
De novo design of picomolar SARS-CoV-2 miniprotein inhibitors.
Science, 2020. doi: 10.1126/science.abd9909

Most Popular Now

Artificial Intelligence in Healthcare Re…

This study presents an overview of the development, adoption and use of Artificial Intelligence (AI) technologies and applications in the healthcare sector across all Member States. The main aim of...

First-of-its-Kind Healthcare Communicati…

A web and mobile app-based start-up launched during the COVID-19 pandemic to help UK healthcare professionals communicate with patients has signed its first commercial agreement with a hospital trust...

Giving AI Penalties to Get Better Diagno…

Anyone waiting for the results of a medical test knows the anxious question: 'Will my life change completely when I know?' And the relief if you test negative. Nowadays, Artificial Intelligence...

New App Helps Parents Identify Treatable…

A ground-breaking new, mobile phone app, 'GrowthMonitor' places the accurate measurement of children's height in the hands of parents and carers. Preliminary data to be presented at the Society for...

DMEA Call for Papers: Digital Health in …

26 - 28 April 2022, Berlin, Germany. Health meets digitalisation. From 26 to 28 April 2022 DMEA - Connecting Digital Health, the leading platform for health IT, is opening its doors...

Health Meets IT: DMEA Newcomer Award Inv…

26 - 28 April 2022, Berlin, Germany. Digitalisation of our healthcare sector must be stepped up - the experience of recent months has shown that. It is why new ideas on...

Bittium Exhibits its High-Tech Medical T…

Bittium exhibits its innovative products and solutions for cardiology and neurophysiology as well as R&D services for the development of medical and healthcare technology at the MEDICA 2021 event. It...

Development of AI Technology for Produci…

Transcranial focused ultrasound can be used to treat degenerative movement disorders, intractable pain, and mental disorders by delivering ultrasound energy to a specific area of the brain without opening the...

Siemens Healthineers and UCSF Create Fir…

Siemens Healthineers and UC San Francisco have formed a research and innovation-driven collaboration to make radiological imaging greener, while improving access to and quality of radiological imaging in Northern California...

Tulane University Study Uses AI to Detec…

A Tulane University researcher found that artificial intelligence (AI) can accurately detect and diagnose colorectal cancer from tissue scans as well or better than pathologists, according to a new study...

Dedalus Acquires Swiftqueue to Support P…

Dedalus Group ("Dedalus"), a leading international healthcare software solutions provider, has announced to have completed the acquisition of 100% of Swiftqueue Technologies Ltd a fast-growing cloud-native appointment and scheduling solution...

FDA Authorizes Marketing of Virtual Real…

The U.S. Food and Drug Administration today authorized marketing of EaseVRx, a prescription-use immersive virtual reality (VR) system that uses cognitive behavioral therapy and other behavioral methods to help with...