Computational synthetic antiviral proteins have been shown to protect human cells from the lab from SARS-CoV-2, the coronavirus that causes COVID-1
In the experiments, the lead antiviral candidate LCB1 competed with the best-known neutralizing SARS-CoV-2 antibodies with regard to its protective effect, as can be seen from the results published in the journal Science.
Researchers at the University of Washington in the United States found that LCB1 is currently being studied in rodents.
Coronaviruses are filled with so-called spike proteins that attach to human cells so that the virus can break in and infect them.
Developing drugs that disrupt this mechanism of entry could lead to the treatment or even prevention of infections, according to the researchers.
They used computers to design new proteins that would bind tightly to the SARS-CoV-2 spike protein, preventing it from infecting cells.
Over two million candidate spike-binding proteins have been developed on the computer. Over 118,000 were then made and tested in the laboratory, they said.
“While extensive clinical testing is still required, we think the best of these computer-generated antivirals show promise,” said lead author Longxing Cao, a postdoctoral fellow at the University of Washington.
“They appear to block SARS-CoV-2 infection at least as well as monoclonal antibodies, but are much easier to make and far more stable, potentially eliminating the need for refrigeration,” added Cao.
The researchers said they created antiviral proteins through two approaches.
First, a section of the ACE2 receptor, to which SARS-CoV-2 binds naturally on the surface of human cells, was built into a series of small protein scaffolds.
Second, completely synthetic proteins have been developed from scratch.
The latter process produced the most potent antivirals, including LCB1, which is approximately six times more potent per mass than the most potent monoclonal antibodies reported to date.
“Our success in developing high-affinity antiviral proteins from the ground up is further evidence that computational protein design can create promising drug candidates,” said senior author David Baker, professor of biochemistry at the UW School of Medicine.
To confirm that the new antiviral proteins are bound to the coronavirus spike protein as intended, the team collected snapshots of the two molecules interacting using cryo-electron microscopy.