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The Coronavirus Could Dodge Some Treatments, Study Suggests

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In a laboratory in New York City, researchers coaxed a key piece of the coronavirus — its infamous outer “spike” — to mutate so that it became invisible to disease-fighting antibodies, according to a new study that has not yet been published in a scientific journal.

The provocative finding should not set off alarm bells, experts said. The altered spikes were not attached to the real coronavirus, which mutates at a much slower pace than most laboratory viruses. But the study does underscore the need for treatments and vaccines that attack the virus in different ways, so that if the pathogen manages to evade one approach, another will be waiting in the wings.

“It’s an old story for virology,” said Dr. Sallie Permar, a virologist and pediatrician at Duke University who was not involved in the study. “If you only target one little region, that virus is going to find a way to get away from it. It’s why viruses are so successful in this world.”

Many vaccines against the coronavirus, as well as several treatments, take aim at its spike protein, the virus’s most potent weapon — and its Achilles’ heel. Without its spikes, the pathogen can’t get into human cells.

Therapies based on this potent protein could stop infections in their tracks. Some promising vaccines, for example, prompt the body to make spike-specific antibodies that might vanquish the virus. And many companies in the race to find coronavirus treatments are making synthetic versions of these molecules, called monoclonal antibodies, to mimic this process en masse.

But all viruses are moving targets. When they replicate, their genetic material doesn’t copy itself perfectly, and mistakes are common. Although most of these mutations are inconsequential, they occasionally lead to noticeable changes in the viruses’ appearance — some of which may disguise them from the immune system. Cavalries of antibodies trained to recognize one version of spike might be totally discombobulated by another, leaving the person vulnerable to disease.

To study these key mutations, a team led by Rockefeller University virologists Theodora Hatziioannou and Paul Bieniasz created synthetic, fast-mutating viruses that carried the coronavirus spike. They then flooded the faux pathogens with different types of monoclonal antibodies known to glom onto the spike, and added healthy cells for the viruses to infect.

When exposed to the deluge of antibodies in the lab, a small proportion of viruses with modified spike proteins eluded the onslaught. Some even managed to replicate inside cells.

“These are the mutations that are potentially problematic,” Dr. Bieniasz said....

 

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