New antiviral small molecule inhibitors disturb interactions between cellular HSP70 and virus proteins

RNA virus outbreaks such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), Ebola virus (EBOV) and Zika virus (ZIKV) causing worldwide health emergencies have highlighted the urgent need of new antiviral strategies. Upon outbreaks with new, unmet viruses where knowledge of virus biology is limited, targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds. Here, we present a strategy to identify novel host-targeted small molecule inhibitors using image-based phenotypic antiviral assay followed by characterization of structure-activity-relationship, mechanism-of-action and molecular targets of the novel antiviral compound using thermal proteome profiling.