The best hopes for a coronavirus drug

Replication is a relatively complicated step, which makes it a ripe target for antivirals. “There’s many, many proteins involved … there’s many potential targets,” says Melanie Ott, a virologist at the Gladstone Institutes and UCSF. For example, remdesivir, an experimental antiviral that is in clinical trials for COVID-19, targets the viral protein that copies the RNA, so the genome-copying step goes awry. Other viral proteins called proteases are necessary to free individual viral proteins that are linked together in one long strand, so they can go off and help the virus replicate as well. And still other proteins might help remodel the internal membranes of the human cell, creating bubbles of membrane that get turned into little virus factories. “The replication machinery sits on these membranes, and then it just starts making tons of viral RNA over and over and over again,” Matthew Frieman, a virologist at the University of Maryland School of Medicine, told me.

In addition to proteins that help it replicate and the spike proteins that make up a portion of the virus’s outer capsule, SARS-CoV-2 has a set of relatively mysterious “accessory proteins” that are unique to this virus. Figuring out what these accessory proteins are doing, Frieman said, could help scientists figure out other ways SARS-CoV-2 interacts with the human cell. These accessory proteins might allow the virus to evade the human cell’s natural antiviral defense in some way—another potential target for a drug. “If you can target that process,” Frieman said, “you can help the cell inhibit the virus.”

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