A bioactive nanocarbon that targets cross-species protein–protein interactions

The quest for bioactive molecules has long been confined to a rather narrow chemical space, limiting the discovery of uncharted chemical structures. Identifying such compounds is essential for uncovering previously unrecognized mechanisms of action and addressing limitations in conventional drug discovery. Here we unveil molecular nanocarbons, nanometer-scale, rigid, π-extended, and carbon-rich/hydrophobic frameworks widely studied in materials science, as a previously untapped class of bioactive agents capable of modulating protein–protein interactions (PPIs). We discovered a molecular nanocarbon that inhibits structurally conserved ligand–receptor pairs in insect diapause signaling (the ligand PND and its receptor PND-2) and human immune signaling (IL-17A and its receptor IL-17RA). The discovered planar nanocarbon compound, named clionene, disrupts both interactions, outperforming the flavonoid cyanidin in potency and selectivity. Structural modeling and molecular dynamics simulations reveal that clionene binds to a hydrophobic pocket at the IL-17A/IL-17RA interface via shape complementarity and π-interactions. These findings establish molecular nanocarbons as bioactive modulators of conserved PPIs, expanding the accessible chemical space for drug discovery and opening unconventional directions in cross-kingdom therapeutic targeting.