Immunoliposomes as a promising antiviral agent against SARS-COV-2

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Resumo

According to the World Health Organization, as of September 13, 2023, there have been approximately 23 million confirmed cases of COVID-19 reported in the Russian Federation, about 400 thousand of which were fatal. Considering the high rate of mutation of the RNA-containing virus genome, which inevitably leads to the emergence of new infectious strains (Eris and Pyrola), the search for medicinal antiviral agents remains an urgent task. Moreover, taking into account the actively mutating receptor-binding domain, this task requires fundamentally new solutions.

This study proposes a candidate immunoliposomal drug that targets the S protein of SARS-CoV-2 by the monoclonal neutralizing antibody P4A1 and ensures the penetration of a highly active ribonuclease into the virus-infected cell, which degrades, among cellular RNA, viral RNA too. We demonstrate a more than 40-fold increase in the neutralizing activity of the developed drug compared to the free monoclonal neutralizing antibody.

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Sobre autores

T. Bobik

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Autor responsável pela correspondência
Email: bobik_tanya@mail.ru
Rússia, Moscow

M. Simonova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

N. Rushkevich

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

N. Kostin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

G. Skryabin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

V. Knorre

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

A. Schulga

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

E. Konovalova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

G. Proshkina

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: bobik_tanya@mail.ru
Rússia, Moscow

A. Gabibov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; M.V. Lomonosov Moscow State University

Email: bobik_tanya@mail.ru

Academician of the RAS

Rússia, Moscow; Moscow

S. Deev

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; National Research University Higher School of Economics

Email: bobik_tanya@mail.ru

Academician of the RAS

Rússia, Moscow; Moscow

Bibliografia

  1. WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int
  2. Widyasari K., Kim J. A review of the currently available antibody therapy for the treatment of coronavirus disease 2019 (COVID-19) // Antibodies. 2023. V. 12. № 1. Р. 5.
  3. Lu L., Ding Y., Zhang Y., et al. Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII // Int. J. Nanomedicine. 2018. V. 13. P. 1927–1944.
  4. Di J., Xie F., Xu Y. When liposomes met antibodies: Drug delivery and beyond // Adv. Drug Deliv. 2020. V. 154–155. P. 151–162.
  5. Park J. W., Kirpotin D. B., Hong K., et al. Tumor targeting using anti-her2 immunoliposomes // Journal of Controlled Release. 2001. V. 74. P. 95–113.
  6. Ott S., Wunderli-Allenspach H. Liposomes and influenza viruses as an in vitro model for membrane interactions I. Kinetics of membrane fusion and lipid transfer // Eur J Pharm Sci. 1994. V. 1. № 6. Р. 323–332.
  7. Guo Y., Huang L., Zhang G., et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes // Nat. Commun. 2021. V. 12. № 1. Р. 2623.
  8. Deyev S., Proshkina G., Baryshnikova O., et al. Selective staining and eradication of cancer cells by protein-carrying DARP in-functionalized liposomes // Eur. J. Pharm. Biopharm. 2018. V. 130. P. 296–305.
  9. Kruglova N., Siniavin A., Gushchin Vol., et al. Different neutralization sensitivity of SARS-CoV-2 cell-to-cell and cell-free modes of infection to convalescent sera // Viruses. 2021. V. 13. P. 1133.
  10. Kostin N. N., Bobik T. V., Skryabin G. A., et al. An ELISA platform for the quantitative analysis of SARS-CoV-2 RBD-neutralizing antibodies as an alternative to monitoring of the virus-neutralizing activity // Acta Nat. 2022. V. 14. P. 109–119.
  11. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays // J Immunol Methods. 1983. V. 65 (1–2). P. 55–63.
  12. Jost C., Schilling J., Tamaskovic R. et al. A. Structural basis for eliciting a cytotoxic effect in HER2-overexpressing cancer cells via binding to the extracellular domain of HER2 // Structure. 2013. V. 21. P. 1979–1991.
  13. Zhang Z., King M. R. Neutralization of the new coronavirus by extracting their spikes using engineered liposomes // Nanomedicine. 2023. V. 50. P. 102674.

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2. Fig. 1. Absorption spectra of liposomes. The red and blue curves are the absorption spectra of barnase–loaded liposomes and empty liposomes, respectively. The lilac curve is the absorption spectrum of barnase loaded into liposomes, which is obtained by subtracting the absorption spectrum of empty liposomes from the absorption spectrum of proteoliposomes.

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3. Fig. 2. Dependence of the luminescence intensity of HEK293T-ACE2 cells expressing the human ACE2 receptor on the surface on the concentration of liposomal preparations in the pseudovirus system.

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4. Fig. 3. Dependence of the luminescence intensity of HEK293T-ACE2 cells expressing the human ACE2 receptor on the surface on the concentration of the P4A1 antibody in liposomal preparations and buffer solution in the pseudovirus system.

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