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

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Abstract

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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About the authors

T. V. Bobik

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

Author for correspondence.
Email: bobik_tanya@mail.ru
Russian Federation, Moscow

M. A. Simonova

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

N. U. Rushkevich

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

N. N. Kostin

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

G. A. Skryabin

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

V. D. Knorre

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

A. A. Schulga

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

E. V. Konovalova

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

G. M. Proshkina

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

Email: bobik_tanya@mail.ru
Russian Federation, Moscow

A. G. 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

Russian Federation, Moscow; Moscow

S. M. 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

Russian Federation, Moscow; Moscow

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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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