MODULAR NANOTRANSPORTERS CAPABLE OF BINDING WITH SARS-COV-2 VIRUS NUCLEOCAPSID PROTEIN INTO TARGET CELLS

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Based on the literature data, an antibody-like molecule, a monobody, was selected that is capable of interacting with the nucleocapsid protein (N-protein) of the SARS-CoV-2 virus with high affinity (dissociation constant 6.7 nM). We have previously developed modular nanotransporters (MNTs) to deliver various molecules to a selected compartment of target cells. In this work, a monobody to the N-protein of the SARS-CoV-2 virus was included in the MNT using genetic engineering methods. In this MNT, a site for the cleavage of the monobody from the MNT in endosomes was also introduced. It was shown by thermophoresis that the cleavage of this monobody from MNT by the endosomal protease cathepsin B leads to a 12-fold increase in the affinity of the monobody for the N-protein. Cellular thermal shift assay showed the ability of the obtained MNT to interact with the N-protein in A431 cells transfected with the SARS-CoV-2 N-protein fused to the mRuby3 fluorescent protein.

Авторлар туралы

Y. Khramtsov

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

A. Ulasov

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

T. Lupanova

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

G. Georgiev

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

A. Sobolev

Institute of Gene Biology, RAS; Lomonosov Moscow State University

Хат алмасуға жауапты Автор.
Email: alsobolev@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

Әдебиет тізімі

  1. Clercq E.D., Li G. // Clin Microbiol Rev. 2016. V. 29. P. 695–747. https://doi.org/10.1128/CMR.00102-15
  2. Gebauer M., Skerra A. // Annu Rev Pharmacol Toxicol. 2020. V. 60. P. 391–415.
  3. Surjit M., Lal S.K. // Infect Genet Evol. 2008. V. 8. P. 397–405.
  4. Wu C., Zheng M. // Preprints. 2020. 2020020247.
  5. Prajapat M., Sarma P., Shekhar N., et al. // Indian J Pharmacol. 2020. V. 52. P. 56.
  6. Du Y., Zhang T., Meng X., et al. // Preprints. 2020.
  7. Sobolev A.S. // Front Pharmacol. 2018. V. 9, 952.
  8. Khramtsov Y.V., Vlasova A.D., Vlasov A.V., et al. // Acta Cryst. 2020. V. D76. P. 1270–1279.
  9. Slastnikova T.A., Rosenkranz A.A., Khramtsov Y.V., et al. // Drug Des Devel Ther. 2017. V. 11. P. 1315–1334.
  10. Li G., Li W., Fang X., et al. // Protein Expr Purif. 2021. V. 186.
  11. Kern H.B., Srinivasan S., Convertine A.J., et al. // Mol Pharmaceutics. 2017. V. 14 (5). P. 1450–1459.
  12. Khramtsov Y.V., Ulasov A.V., Lupanova T.N. et al. // Dokl Biochem Biophys. 2022. V. 506. P. 220–222.
  13. Molina D.M., Jafari R., Ignatushchenko M., et al. // Science. 2013. V. 341. P. 84–87.
  14. Liao H.-I., Olson C.A., Hwang S., et al. // J Biol Chem. 2009. V. 284. P. 17512–17520.

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
2.

Жүктеу (439KB)
3.

Жүктеу (76KB)
4.

Жүктеу (94KB)

Осы сайт cookie-файлдарды пайдаланады

Біздің сайтты пайдалануды жалғастыра отырып, сіз сайттың дұрыс жұмыс істеуін қамтамасыз ететін cookie файлдарын өңдеуге келісім бересіз.< / br>< / br>cookie файлдары туралы< / a>