Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Intracellular Degradation of SARS-CoV-2 N-protein Caused by Modular Nanotransporters Containing Anti-N-protein Monobody and a Sequence that Recruits the Keap1 E3 Ligase

Yuri V. Khramtsov
,
Alexey V. Ulasov
ORCID logo ,
Tatiana N. Lupanova
,
Tatiana A. Slastnikova
,
Andrey A. Rosenkranz
ORCID logo ,
Egor S. Bunin
,
Georgii P. Georgiev
,
Alexander S. Sobolev
*
Version 1 : Received: 3 November 2023 / Approved: 3 November 2023 / Online: 3 November 2023 (14:35:15 CET)

A peer-reviewed article of this Preprint also exists.

Khramtsov, Y.V.; Ulasov, A.V.; Lupanova, T.N.; Slastnikova, T.A.; Rosenkranz, A.A.; Bunin, E.S.; Georgiev, G.P.; Sobolev, A.S. Intracellular Degradation of SARS-CoV-2 N-Protein Caused by Modular Nanotransporters Containing Anti-N-Protein Monobody and a Sequence That Recruits the Keap1 E3 Ligase. Pharmaceutics 2024, 16, 4. Khramtsov, Y.V.; Ulasov, A.V.; Lupanova, T.N.; Slastnikova, T.A.; Rosenkranz, A.A.; Bunin, E.S.; Georgiev, G.P.; Sobolev, A.S. Intracellular Degradation of SARS-CoV-2 N-Protein Caused by Modular Nanotransporters Containing Anti-N-Protein Monobody and a Sequence That Recruits the Keap1 E3 Ligase. Pharmaceutics 2024, 16, 4.

Abstract

In addition to nucleic acids, various viral proteins are involved in the assembly of virion. If it is possible to create a biologically active agent that leads to the degradation of one of the key proteins for virus assembly and/or destroys the viral factory, then this agent will effectively cope with virus replication. One of these key proteins for the SARS-CoV-2 virus is the nucleocapsid protein (N-protein). As such a bioactive agent, we offer a modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic to the N-protein, contains an amino acid sequence for the attraction of the Keap1 E3 ubiquitin ligase. This should lead to the subsequent degradation of the N-protein. We have shown that functional properties of modules within the MNT permit its internalization into target cells, endosome escape into the cytosol, and binding to the N-protein. Using flow cytometry and Western blot, it was demonstrated that significant degradation of N-protein is observed when A549 and A431 cells transformed with N-protein are incubated with the developed MNTs. The proposed MNTs open up a new approach for the treatment of viral diseases.

Keywords

modular nanotransporters; Keap1E3 ligase; N-protein degradation; SARS-CoV-2 virus; flow cytometry; Western blot; intracellular concentrations; thermophoresis; cathepsin B

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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