By subtly tweaking the structure of the natural product prostratin, chemists have come up with molecules that could help eradicate AIDS (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1302634110). The current antiretroviral cocktail used to treat HIV only attacks active virus. People must take these drugs for life because the virus also adopts a dormant provirus form, which hides in immune cells and can emerge as active virus. Certain natural products, such as prostratin, can coax dormant provirus out of hiding. By using such compounds, doctors could flush HIV from a patient’s system and effectively cure the disease. Paul A. Wender of Stanford University, Tae-Wook Chun of the National Institutes of Health, and Jerome A. Zack of the University of California, Los Angeles, have come up with prostratin analogs that are more potent than the parent compound. The molecules can be made in seven steps from phorbol, a component of croton oil, which comes from the seeds of a tropical shrub. At nanomolar concentrations, one of the compounds (shown) ferreted the virus out of immune cells from HIV-positive patients taking the antriretroviral cocktail. It took 100 times as much prostratin, currently a preclinical drug candidate, to do the same job.