More than 35 mil­lion people around the world now live with HIV/ ​AIDS. While drug dis­covery efforts to combat the dis­ease have been suc­cessful, mul­tiple treat­ments are required because the virus mutates and develops resis­tance to indi­vidual drugs. In fact, the HIV virus has evolved to evade the first line of defense—a pro­tein called APOBEC3G, also known as A3G. Now, in a paper pub­lished last week in the journal Nature Chem­istryphysics pro­fessor Mark Williams and his team present new research that elu­ci­dates a long-​​held paradox about these pro­teins that could trans­form HIV drug discovery.