Computer-Aided Search for Novel Anti-Hiv-1 Agents Presenting Peptidomimetics of Neutralizing Antibodies and Evaluation of their Potential Inhibitory Activity by Molecular Modeling

Based on the analysis of the structural complexes between the HIV-1 V3 loop peptides from different viral modifications and the Fab-fragment of a broadly neutralizing monoclonal antibody (mAb) 3074, computer-aided search for chemical compounds able to imitate the pharmacophore properties of the antigen-binding site of this antibody was carried out. Evaluation of the binding efficacy of these compounds to the V3 loop peptides was performed by molecular docking followed by selection of the most probable peptidomimetics of mAb 3074. Using molecular dynamics and free energy calculations, it was shown that, similarly to mAb 3074, the selected compounds exhibit a high affinity to the immunogenic tip of the HIV-1 V3 loop forming conserved structural motif, which contains residues critical for cell tropism. In this context, these compounds are considered as the promising basic structures for the design of novel, potent and broad anti-HIV-1 drugs.