It’s not easy to spot filopodia. Thin wisps of protein less than a micrometer across, they dangle from the surface of a cell, probing its surroundings much as we might grope our way around a darkened room. Usually, they help the cell explore and communicate with its neighbors. But recently, a team of researchers imaging cells infected with SARS-CoV-2 noticed some strange filopodia behavior. Seen through an electron microscope, the filopodia resembled the sprouting tubers of a long-abandoned potato. The tendrils were gnarled and extended, branching outwards at the tips. And all along them were buds of the virus. They seemed to be hitching a ride—part of their onward journey to nearby cells.
Everything You Need to Know About the CoronavirusHere's all the WIRED coverage in one place, from how to keep your children entertained to how this outbreak is affecting the economy. The discovery of these unusual filopodia was, according to Nevan Krogan, a systems biologist at UC San Francisco, largely by happenstance: His team had been searching for drugs that might hamper the virus’s ability to turn cells into replication factories. To do that, they look for changes that occur in infected cells—which proteins fade or multiply, which cellular processes are turned off or on—deciphering how the virus goes about its hijacking. Then they look for drugs that throw a wrench into the virus’s plans. In particular: old drugs, which have already been approved to treat other diseases or are on their way to it. The results from the team’s recent search are expected to publish Saturday in the journal Cell.
Krogan’s team—a vast collaboration that includes dozens of researchers around the world—is one of a number of groups engaged in a strategy known as drug repurposing. The idea is to short-circuit the long road to a new treatment. It works, in part, because many existing drugs are fairly blunt instruments, exploiting weaknesses that are common across different pathogens. Take remdesivir, which was developed by Gilead over a decade ago to treat Ebola patients. In that quest, it failed. But now there’s evidence it can help treat Covid-19 . Other repurposing efforts take advantage of the common ways the body responds to different pathogens. That’s the story for dexamethasone, an old steroid normally used for ailments like croup that the UK’s Recovery trial recently found effective in calming the overactive immune response in critically-ill Covid-19 patients.
To find promising candidates, researchers often comb through libraries of thousands of compounds and apply doses of them to infected cells, looking for ones that get rid of the virus at a safe dosage. But Krogan argues that the process can be more targeted than that. While a brute force approach may eventually yield a hit, the less you know about how a particular drug works, the more hurdles lie ahead. He points to the antimalaria drug hydroxychloroquine, which worked well in a dish, but turned out to be no better than a placebo in preventing Covid-19 infections among exposed people. “There are thousands of people testing hydroxychloroquine without understanding what it does,” he says. “It kind of drives me crazy.” So instead, the team tries to develop leads by examining how the virus rewires a cell’s basic biology, turning off some functions while amplifying others.
In an initial study, published in April in the journal Nature, Krogan’s team examined the interactions between proteins in the virus and human cells, then looked for drugs that would interfere. They published a map of those interactions, which researchers and drug companies have scoured for candidates for further animal studies and clinical trials.
Already, since Tuesday, the number of diagnosed coronavirus patients in Wuhan has shot up to 729.Using case data scraped from official reports, a team led by Jonathan Read at Lancaster University plotted a temporal map of the coronavirus’s spread, starting on January 1, when local authorities closed the meat-and-animal market where the virus is believed to have crossed into humans from an unknown source .