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The RNA genome of HIV-1 is encapsidated as a dimer.The two single strands are held together by the formation of a loop-loop complex (or kissing complex) at a specific Dimerization Initiation Site (DIS).We had solved the DIS crystal structure [1] and we noticed that the DIS bears a strong,and probably fortuitous,resemblance with the Aminoacyl-decoding site (A-site) within bacterial ribosomes.Since this A-site is the target of natural aminoglycoside antibiotics we predicted that this also holds true for the DIS [2].This prediction was fully verified and we were able to co-crystallize different antibiotics (neamine,neomycin,paromomycin,ribostamycin,lividomycin) with two DIS variants (subtypes A and F).Biophysical studies (UV-melting and IsoThermal μ Calorimetry:ITC) yielded information on the stabilization of the DIS loop-loop complex in presence of antibiotics and about the affinity of these antibiotics for the DIS [3].Remarkably,neomycin binds to the DIS more tightly (Kd=0.1 μM) than to the A-site which is its natural target (Kd=l.5 μ M).ITC gave a clear picture of the difference between specific antibiotics binding to the DIS RNA binding site,and unspecific binding to the whole RNA mediated mostly by electrostatic interactions.We also showed by ex-vivo studies that the DIS can be specifically targeted by these antibiotics in infected cells [4].