Abstract
Modular nanotransporters (MNTs) containing an antibody-like molecule, monobody, to the N‑protein of the SARS-CoV-2 virus, as well as an amino acid sequence that recruits the Keap1 E3 ligase (E3BP) were created. 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 a basis for the creation of new antiviral drugs against the SARS-CoV-2 virus.
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ACKNOWLEDGMENTS
The experiments were performed using the equipment of the Core Facility of the Institute of Gene Biology, Russian Academy of Sciences.
Funding
This study was supported by the Russian Science Foundation (project no. 21-14-00130).
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Translated by M. Batrukova
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Khramtsov, Y.V., Ulasov, A.V., Lupanova, T.N. et al. Modular Nanotransporters Capable of Causing Intracellular Degradation of the N-Protein of the SARS-CoV-2 Virus in A549 Cells with Temporary Expression of This Protein Fused with a Fluorescent Protein mRuby3. Dokl Biochem Biophys 513 (Suppl 1), S60–S62 (2023). https://doi.org/10.1134/S1607672923700710
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DOI: https://doi.org/10.1134/S1607672923700710