¹Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
²United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, Republic of Belarus
³Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, China

Abstract. Six potential peptidomimetics of the cross-reactive neutralizing anti-HIV-1 antibody N6 that are able to mimic the pharmacophoric features of this immunoglobulin by specific and effective interactions with the CD4-binding site of the viral gp120 protein were identified by virtual screening and molecular modeling. The key role in the interaction of these compounds with gp120 is shown to play multiple van der Waals contacts with conserved residues of the gp120 Phe-43 cavity critical for the HIV binding to cellular receptor CD4, as well as hydrogen bond with Asp-368gp120 that increase the chemical affinity without activating unwanted allosteric effect. According to the data of molecular dynamics, the complexes of the identified ligands with gp120 are energetically stable and show the lower values of binding free energy compared with the HIV-1 inhibitors NBD-11021 and DMJ-II-121 used in the calculations as a positive control. Based on the data obtained, it was concluded that the identified compounds may be considered as promising candidates for detailed experimental studies to their further use in the design of novel antiviral drugs presenting HIV-1 inhibitors that block the early stages of the development of HIV infection.

Key words: HIV-1, gp120 protein, HIV-1 entry inhibitors, virtual screening, molecular docking, quantum chemical calculations, molecular dynamics, anti-HIV drugs.