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Changes in S-protein conformations of coronaviruses as a cause of antibody-dependent enhancement of infection

Nechipurenko Yu.D., Anashkina A.A., Yegorov E.E, Semyonov D.A.1, Matveeva O.V.2

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia

1Institute of Biophysics, Institute of Biophysics, Siberian Branch of Russian Academy of Science., Akademgorodok 50, Krasnoyarsk, 660036 Russia

2Sendai Viralytics LLC, Acton, MA 01720 USA

Binding the virus to suboptimal antibodies that are not neutralizing can induce the virus to enter the cells of the immune system, where the virus, instead of being inactivated, begins to replicate and kills the immune cell. This phenomenon is called antibody-dependent infection enhancement (or ADE for «antibody dependent enhancement». It is indicated for a number of viruses, including coronaviruses. For coronaviruses, in particular for SARS-CoV-1 (SARS-CoV), it has been shown that antibodies to the spiked S-protein can provoke ADE [1-4]. We believe that changes in the antigenic determinants of this protein may lead to a decrease in the binding strength of neutralizing antibodies to the virus, turning them into suboptimal – non-neutralizing, ADE-capable antibodies. It is possible that ADE is affected not only by structural rearrangements of the S protein, but also by the dynamics of changes in its conformations. According to our hypothesis, ADE may occur during SARS-CoV-2 viral infection and explain the severe course of the disease in some infected people [4,5]. The binding of antibodies to the virus occurs in the extracellular environment, getting into the immune cell. during phagocytosis, complexes of antibodies with viruses can appear in an environment with other properties (pH, ionic strength), and thus the affinity and avidity of antibodies can change [6-8]. It is possible that a decrease in the pH of the extracellular environment, characteristic of patients with COVID-19, may contribute to ADE. However, acidosis can affect the stability of antibody complexes with viruses and contribute to their destruction in the extracellular environment and without ADE. A systematic view of the COVID-19 disease requires the involvement of ideas from different areas of medical Biophysics.

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