Researchers engineer a tiny antibody capable of neutralizing the coronavirus

At 2 a.m. one night last April, Michael Schoof triple-checked the numbers on his screen, took a deep breath, and fired off an email he’d been waiting all day to send.

«I think it’s working» was the cautious wording of his message.

Schoof, a graduate student in the lab of Peter Walter, Ph.D., a renowned scientist specializing in protein sorting and cellular membranes, was part of a small team on a quixotic mission: to immobilize SARS-CoV-2, the novel coronavirus that causes COVID, by using a synthetic version of tiny antibodies originally discovered in llamas and camels. These «nanobodies,» as they’re known, had come from the UC San Francisco lab of Aashish Manglik, M.D., Ph.D., an up-and-coming protein scientist who had spent the previous three years building a vast library of nanobodies and developing new ways to exploit their unusual properties.

During the previous month, Schoof had spent most of his waking hours cloistered in the otherwise empty lab complex on UCSF’s Mission Bay campus. It was the height of COVID’s spring 2020 surge, and only essential health care staff and those working on science related to the pandemic were allowed into the University’s facilities. Schoof had dragooned his roommate, a fellow grad student named Reuben Saunders, into working with him on the project. Subsisting on steamed dumplings and gallons of tea, they had been sorting through the 2 billion nanobodies in Manglik’s library in the hope of identifying a molecule capable of glomming on to the deadly SARS-CoV-2 and immobilizing it. Now, finally, Schoof was convinced they had achieved their first big breakthrough.

The first step in any viral infection is a cellular hijacking. To gain control of a human cell, SARS-CoV-2 latches the grappling-hook-like spikes on its own exterior to proteins called ACE2 receptors on the exterior of a target cell. But what if, the researchers wondered, they could block the hijacker by giving the grappling hooks something else to latch onto?

That day, Schoof had begun running tests on hundreds of colonies of yeast, each engineered to produce certain nanobodies from Manglik’s library. All of these particular nanobodies had demonstrated an ability to latch onto SARS-CoV-2’s spikes. Now it was time to ask the key questions: How tightly had these nanobodies bound to the spikes? Were they able to compete with the ACE2 receptors?

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Πηγή: phys.org

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