Change of Antigenic Determinants of SARS-CoV-2 Virus S-Protein as a Possible Cause of Antibody-Dependent Enhancement of
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Change of Antigenic Determinants of SARS-CoV-2 Virus S-Protein as a Possible Cause of Antibody-Dependent Enhancement of Virus Infection and Cytokine Storm Yu. D. Nechipurenkoa, *, A. A. Anashkinaa, and O. V. Matveevab, c aEngelhardt
Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia b Sendai Viralytics LLC, Acton, MA 01720 USA c Biopolymer Design LLC, Acton, MA 01721 USA *e-mail: [email protected] Received May 28, 2020; revised May 28, 2020; accepted June 5, 2020
Abstract—A hypothesis is proposed that the cytokine storm syndrome, which complicates COVID-19 in some patients, is a consequence of antibody-dependent enhancement of virus infection, which is in turn happens due to a change in dominant antigenic determinants of SARS-CoV-2 S-protein. The antibody-dependent enhancement of virus infection is a phenomenon in which virus-specific antibodies that are not neutralizing enhance the entry of infectious virus into immune cells causing their death. Antibody-dependent enhancement has been reported for different coronaviruses. This phenomenon happens due to a decrease in the binding strength of neutralizing antibodies to the virus, which converts these antibodies into suboptimal— not neutralizing ones. According to our hypothesis, such a decrease in affinity may be associated with a change in the conformation of the viral S-protein. We believe that this conformational change is the major factor in the switching of antibodies affinity, which triggers antibody-dependent enhancement. However, other factors that contribute to antigen drift and antigenic determinant changes may also play a role. Keywords: COVID-19, coronavirus, SARS-CoV-2, antigen-dependent enhancement of infection, ADE, spike protein, S-protein, change in conformations, antigenic determinants, change in epitopes DOI: 10.1134/S0006350920040119
INTRODUCTION The SARS-CoV-1 and SARS-CoV-2 viruses infect host cells via the ACE2 receptor [1]. However, the SARS-CoV-1 can enter cells that are lacking this receptor using alternative cell entry strategy that is called antibody-dependent enhancement of viral infection (ADE) [2–4]. ADE phenomenon is described for different viruses but it is more common for viruses, which genomes are represented by the (+) RNA strand [5], including coronaviruses [1, 2, 7–9]. ANTIBODY DEPENDENT DISEASE ENHANCEMENT Figure 1 shows a scheme that visualizes ADE phenomenon for coronaviruses (right) by contrasting it with an efficient immune response that promotes virus clearance (left). Both types of responses involve complex formation of IgG antibodies with a virus that via FcyII receptors can be absorbed by CD32+ immune cells [6, 8, 10–13]. However, this process might lead to the destruction of a virus inside an immune cell [10] or to intracellular viral replication [2, 3, 6–8]. During the process that results in efficient immune response, the
virus cannot escape a complex that is formed with high affinity neutralizing antibodies – and is getting destroyed by cellular proteases and RNases [10]. Thus,
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