Nordic Life Science 1
SCIENCE ARTICLE Q4 2019 the common cold, and more
are caused by enteroviruses and rhinoviruses. For 32 years, scientists knew of one druggable target on the surface of these picornavirus family members. An international team just discovered another. Fitting compounds into this target, which is a pocket at the junction of viral capsid proteins, locks the viruses shut so they can’t replicate. “Picornaviruses are common and we’re fighting them all the time,” says University of Helsinki Professor Sarah Butcher, who led the structural work reported in PLOS Biology. Her colleagues in India and Belgium first identified viral inhibitors by computational design and tested them in large-scale, cell-based viral screening assays. Data, including on resistant mutants, suggested the best compound targeted the viral surface. Butcher’s group used cryoelectron microscopy (cryoEM), a method recognized by a 2017 Nobel Prize, to discover the inhibitor binding site. “The cryoEM field has been developing tremendously over the past five years or so,” Butcher says. “We could clearly see a pocket where the drug bound and we mapped changes in resistant viruses to the binding site. NORDICLIFESCIENCE.ORG 85