Deciphering the significance of blood group in SARS-CoV-2 infection using atomic force microscopy

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 in China, scientists have been researching what factors are involved in the infection of SARS-CoV-2, the causal pathogen of Coronavirus Disease 2019. Among several risk factors, the potential influence of ABO blood types has been approached by many scientific researchers. One of the possible mechanisms explaining the role of blood type antigens in SARS-CoV-2 infection is the crucial role of glycans, including human blood group antigens, on the virions landing on the cell surface. Indeed, as obligate intracellular parasites, viruses initiate their life cycle from their binding on the surface of host cells. Also, the viral attachment may be a relatively nonspecific process using ubiquitously expressed receptors, including glycoproteins and lipids. Indeed, binding to attachment factors increases the probability of the virus finding its entry receptors that are not abundant on the cell surface. This thesis investigates which ABO blood group antigen could serve as binding partner facilitating SARS-CoV-2 attachment to the host cell entry receptors. To this end, atomic force microscopy was used to quantitatively define the thermodynamic and kinetic parameters of SARS-CoV-2 binding to the blood group antigens at the single-molecule level. Once the experimental conditions were optimized, we showed that the spike protein of SARS-CoV-2 specifically engages the blood group A antigen on model surfaces with a dissociation constant in the nanomolar range, suggesting a low to moderate affinity. Then, the preferential binding towards blood group A was confirmed on living cells. Finally, we observed that a blood group A antigen – mediated SARS-CoV-2 binding is independent of its binding to the angiotensin-converting enzyme 2 entry receptor. These results allow us to gain better insight into the early step of the SARS-CoV-2 infection mechanism and lead us to a prime interest in developing antiviral strategies.