HIV hijacks healthy T cells by fusing with them and making them replicate the deadly virus. The complex process requires a protein on the virus’s outer covering to bind with a receptor and coreceptor on the T cell. In some T cells, the coreceptor is CCR5, and in others, it’s CXCR4. No single drug available today blocks both of these coreceptors, so Dennis C. Liotta and colleagues at Emory University wondered whether they could come up with one. They overlaid the structures of CCR5 and CXCR4 and found a structurally similar binding motif in both coreceptors. They then virtually screened small molecules and found some that should block both coreceptors. Anthony Prosser, a graduate student in Liotta’s lab, devised a synthesis of one such compound and made many analogs (example shown). The molecules not only inhibited HIV’s binding to both CCR5 and CXCR4, but they also blocked HIV reverse transcriptase, an enzyme that’s key to the virus’s ability to copy itself. Liotta noted that the compounds are still in early development, but if successful, they could lead to a low-cost HIV treatment.