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 Phe43 cavity critical for the HIV binding to cellular receptor CD4, as well as hydrogen bonds 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. The identified compounds may be involved in the design of novel antiviral drugs presenting HIV-1 inhibitors that block the early stages of the development of HIV infection.
Docking-based virtual screening and identification of potential COVID-19 main protease inhibitors from brown algae