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Dear Readers, Welcome to the latest issue of The Magazine
Computer-designed synthetic antiviral proteins have been shown to protect lab-grown human cells from SARS-CoV-2, the coronavirus that causes COVID-19, scientists say.
From the experiments, the lead antiviral candidate, called LCB1, rivalled the best-known SARS-CoV-2 neutralising antibodies in its protective activities, according to the findings published in the journal Science.
The researchers at the University of Washington in the US noted that LCB1 is now being evaluated in rodents.
Coronaviruses are studded with so-called Spike proteins, which latch onto individual cells to enable the virus to break in and infect them, they said.
The development of drugs that interfere with this entry mechanism could lead to treatment of or even avoidance of disease, according to the researchers.
They used computers to create new proteins which bind tightly to SARS-CoV-2 Spike protein and block it from infecting cells.
Over two million candidate Spike-binding proteins were designed on the computer. More than 118,000 were then produced and analyzed in the lab, they said.
“Although extensive clinical testing is still needed, we consider the best of these computer-generated antivirals are very promising,” said lead author Longxing Cao, a postdoctoral scholar in the University of Washington.
“They seem to block SARS-CoV-2 infection at least as well as monoclonal antibodies, but are a lot easier to produce and far more stable, possibly eliminating the need for refrigeration,” Cao added.
The researchers said they created antiviral proteins via two approaches.
First, a sector of the ACE2 receptor, which SARS-CoV-2 naturally binds to on the surface of human cells, was integrated into a set of small protein scaffolds.
Second, completely synthetic proteins were created from scratch.
The latter method produced the most potent antivirals, including LCB1, which is approximately six times more potent on a per mass basis compared to the most effective monoclonal antibodies reported thus far.
“Our success in designing high-affinity antiviral proteins from scratch is additional proof that computational protein design can be used to make promising drug candidates,” said senior author David Baker, professor of biochemistry at the UW School of Medicine.
To confirm that the new antiviral proteins attached to the coronavirus Spike protein as planned, the team collected snapshots of the two molecules interacting by using cryo-electron microscopy.
