Modular nanotransporters capable of cause intracellular degradation of the N-protein of the SARS-CoV-2 virus in A549 cells with temporary expression of this protein fused with the fluorescent protein <i>mRuby3</i>

Abstract

Modular nanotransporters (MNTs) have been created containing an antibody-like molecule, monobody, to the N-protein of the SARS-CoV-2 virus, as well as an amino acid sequence that attracts the E3 ligase Keap1 (E3BP). This MNT also included a site for cleavage of the E3BP monobody from the MNT in acidic endocytic compartments. It was shown that this cleavage by the endosomal protease cathepsin B leads to a 2.7-fold increase in the affinity of the E3BP monobody for the N-protein. Using A549 cells with transient expression of the N-protein fused with the fluorescent protein mRuby3, it was shown that incubation with MNT leads to a significant decrease in mRuby3 fluorescence. It is assumed that the developed MNTs can serve as the basis for the creation of new antiviral drugs against the SARS-CoV-2 virus.