Computer-aided design of the potential drugs for AIDS therapy: $\beta$-galactosylceramide and the HIV-1 gp120 V3 Loop

Computer-aided design of two water-soluble analogs of $\beta$-galactosylceramide ($\beta$-GalCer), which present potential HIV-1 entry inhibitors, was implemented by the analysis of intermolecular interactions of $\beta$-GalCer with the central region of the virus V3 loop. As a result, interactions of overlapping $\pi$-orbitals of the side chain of the conserved phenylalanine, which resides in its immunogenic tip Gly-Pro-Gly-Gln/Arg-Ala-Phe, with the XH (X=C or O) sugar groups was suggested to play a key role in forming the structural complexes of glycolipids with the HIV-1 V3 loop. At the same time, hydrogen bonds between galactose hydroxyl groups and polar atoms of the V3 backbone were also illustrated to greatly contribute to the stabilization of the complexes of interest. Using binding energy simulations carried out for the glycolipids and V3 loop peptides, the high probability of exhibiting of antiviral activity was predicted for the designed $\beta$-GalCer analogs.