After more than a year of anxiety and tragedy, COVID-19 vaccines have given us hope again. But vaccines are only part of the equation; we also need treatments to prevent severe disease after infection. The FDA has approved three antibody-based therapies in the last year.

COVID-19 vaccines have restored our optimism following more than a year of anxiety and tragedy. But vaccines are only one side of the coin—we also need treatments that can prevent severe disease after someone has been infected. Significant progress has been made in the last year toward developing effective antibody-based therapies, and the Food and Drug Administration has approved three drugs for emergency use (EUA).

Sotrovimab, the latest antibody therapy, was developed by GlaxoSmithKline and Vir Biotechnology following the discovery of a naturally occurring antibody (in the blood of a COVID-19 survivor) with remarkable breadth and efficacy in a large collaborative study conducted by scientists from across the country.

Experiments have demonstrated that this antibody, named S309, neutralises all known COVID-19 variants — including newly emerged strains that can now “escape” previous antibody therapies — as well as the closely related original SARS-CoV virus.

During an early phase of the study, Jay Nix, the leader of the Molecular Biology Consortium based at Berkeley Lab’s Advanced Light Source (ALS), used beamlines at the ALS and at SLAC’s Stanford Synchrotron Radiation Lightsource to perform X-ray crystallography on samples of survivor-derived antibodies.

Along with other crystallography and cryo-electron microscopy findings, his work contributed to the generation of detailed structural maps of how these antibodies bind to the SARS-CoV-2 spike protein, enabling the larger team to prioritise the most promising candidates for cell culture and animal studies. Following promising laboratory results, the developers designed and evaluated sotrovimab based on the structure of S309.

The FDA approved sotrovimab in late May following trials that demonstrated that people with mild to moderate COVID-19 infections who received an infusion of the therapy experienced an 85 percent reduction in hospitalisation or death when compared to those who received a placebo.

But the researchers didn’t stop there.

Recognizing the possibility of new mutations and the emergence of a novel pathogenic coronavirus as a result of an animal-human crossover event, the researchers initiated a follow-up study to elucidate the factors that contribute to antibodies being resistant to viral escape and how certain antibodies are also broadly reactive against diverse, related viruses.

They identified an antibody with unprecedented universal potency using biochemical and structural analysis, deep mutational scanning, and binding experiments.

“This antibody, which binds to a previously unknown site on the coronavirus spike protein, appears to neutralize all known sarbecoviruses—the genus of coronaviruses that cause respiratory infections in mammals,” said Nix, who is an affiliate in Berkeley Lab’s Biosciences Area.

“And, due to the unique binding site on mutation-resistant part of the virus, it may well be more difficult for a new strain to escape.”

Subsequent tests in hamsters indicate that if given prophylactically, this antibody may even prevent COVID-19 infection.

The new work was published in Nature.

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