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.
The discovery of these unusual filopodia was, according to Nevan Krogan, a systems biologist at UC San Francisco’s Quantitative Biosciences Institute, 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.
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.
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.
Of particular interest, he adds, is testing combinations of compounds, noting the success of the three-drug cocktail currently used to treat HIV. Perhaps they’ll try one of these compounds they identified along with remdesivir, to see if it improves the virus-clearing effects at a lower dose. “By doing the biology first, you can be so much more intelligent when you get to specific combinations,” he says. “The more you know about your foe, the easier it is to defeat.”
https://www.wired.com/story/old-drugs-could-reveal-a-new-way-to-attack-the-coronavirus/HELP US SPREAD GOOD NEWS!
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