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 mRuby3

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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.

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Y. Khramtsov

Institute of Gene Biology, RAS

编辑信件的主要联系方式.
Email: alsobolev@yandex.ru
俄罗斯联邦, Moscow

A. Ulasov

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
俄罗斯联邦, Moscow

T. Lupanova

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
俄罗斯联邦, Moscow

G. Georgiev

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru

Academician

俄罗斯联邦, Moscow

A. Sobolev

Institute of Gene Biology, RAS; Lomonosov Moscow State University

Email: alsobolev@yandex.ru

Corresponding 

俄罗斯联邦, Moscow; Moscow

参考

  1. Clercq E.D., Li G. // Clin Microbiol Rev. 2016. V. 29. P. 695–747.
  2. Gebauer M., Skerra A. // Annu Rev Pharmacol Toxicol. 2020. V. 60. P. 391-415.
  3. Shipunova V.O., Deyev S.M. // Acta Naturae. 2022. V. 14. № 1(52). P. 54–72.
  4. Tolmachev V.M., Chernov V.I., Deyev S.M. // Russ Chem Rev. 2022. V. 91. № 3. RCR5034
  5. Surjit M., Lal S.K. // Infect Genet Evol. 2008. V. 8. P. 397–405.
  6. Wu C., Zheng M. // Preprints. 2020. 2020020247.
  7. Prajapat M., Sarma P., Shekhar N., et al. // Indian J Pharmacol. 2020. V. 52. P. 56.
  8. Du Y., Zhang T., Meng X., et al. // Preprints. 2020. doi: 10.21203/rs.3.rs-25828/v1.
  9. Khramtsov Y.V., Ulasov A.V., Lupanova T.N., et al. // Dokl Biochem Biophys. 2023. V. 510. P. 87–90.
  10. Lu M., Liu T., Jiao Q. et al. // Eur J Med Chem. 2018. V. 146. P. 251–259.
  11. Fulcher L.J., Hutchinson L.D., Macartney T.J., et al. // Open biology. 2017. V. 7. 170066.
  12. Slastnikova T.A., Rosenkranz A.A., Khramtsov Y.V., et al. // Drug Des Devel Ther. 2017. V. 11. P. 1315–1334.
  13. Khramtsov Y.V., Ulasov A.V., Lupanova T.N., et al. // Dokl Biochem Biophys. 2022. V. 506.
  14. Kern H.B., Srinivasan S., Convertine A.J., et al. // Mol Pharmaceutics. 2017. V. 14(5). P. 1450–1459.
  15. Wang S., Dai T., Qin Z., et al. // Nat. Cell Biol. 2021. V. 23. P. 718–732.

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2. Fig. 1. Dependence of the relative fluorescence intensity (the fluorescence intensity before the start of thermophoresis is taken as 100%) 20 s after the start of thermophoresis on the concentration of MNT1 or cleaved MNT1 at a constant concentration of N-protein labeled with AF488 (5 nM). The standard error of relative fluorescence intensity determination is indicated (14–17 replicates).

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3. Fig. 2. Relative fluorescence of A549 cells (the fluorescence of cells to which MNT was not added was taken as 100%) when they were incubated for various times with 500 nM MNT1 or 500 nM MNT0. Mean values with corresponding standard error are shown (n = 3–9).

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