When inhibition of paramyxovirus family members was assessed, six compounds efficiently blocked the closely related canine distemper virus (CDV) and the more distantly related human parainfluenzavirus type 3 (HPIV3) in addition to MeV-Alaska, while leaving cell metabolic activity essentially unaffected [19] . Of these independent hits, three share a common molecular scaffold ( [19] and figure 1A ). Since HTS scores of these analogs best matched the target criteria and antiviral activity was highest in this group [19] , we subjected them to further characterization and developmental efforts. Synthetic optimization and structural confirmation of the scaffold returned a lead analog JMN3-003 (figures 1B and S1), which showed potent activity against MeV, a selection of clinically significant members of the para-and orthomyxovirus families, and, albeit to a lesser degree, representatives of positive strand RNA virus (sindbis virus of the Alphaviridae) and DNA virus (vaccinia virus of the Poxviridae) families (figure 1C, inhibitory concentrations for a larger panel of myxovirus family members are summarized in table 1). As observed for the primary hit compound, metabolic activity of different established cell lines exposed to JMN3-003 was unchanged at 75 mM, the highest assessable concentration based on solubility of the substance in growth media (figure 1D and  table 1 ). Of different primary human cells examined, metabolic activity was unaffected (PBMCs, smooth muscle cells) or only slightly affected (bronchial epithelial cells) by the compound ( figure 1E ). These data support potent anti-myxovirus activity of the compound with active concentrations ranging from 10 to 80 nM depending on the target virus.